No full-text available
To read the full-text of this research,
you can request a copy directly from the author.
The hippocampal continuation (indusium griseum): Its connectivity in the hedgehog tenrec and its status within the hippocampal formation of higher vertebrates
Abstract
The indusium griseum and its precallosal extension are usually considered poorly differentiated portions of the hippocampus. The connections of this so-called 'hippocampal continuation' (HCt) have only been analyzed so far in rodents, which show one of the least-developed HCt among mammals. In this study we have investigated the relatively well differentiated HCt of the small Madagascan hedgehog tenrec (Afrotheria) using histochemical and axonal transport techniques. The tenrec's HCt shows associative and commissural connections. It receives laminar specific afferents from the entorhinal cortex (collaterals from neurons projecting to the dentate area), the anterior and posterior piriform cortices as well as the supramammillary region. A few fibers also originate in the olfactory bulb and the dentate hilus. Among these input areas only the dentate hilus receives a significant reciprocal projection from the HCt. Additional HCt efferents are directed to the subcallosal septum (presumed septohippocampal nucleus), the olfactory tubercle and the islands of Calleja. With the exception of the supramammillary afferents and possible efferents to the supraoptic nucleus we failed, however, to demonstrate distinct thalamic and hypothalamic connections. A comparison of the connections of the HCt with those of the hippocampal subdivisions reveal some similarity between the HCt and the dentate area, but the overall pattern of connectivity does not permit a correlation of the HCt with the dentate area, let alone the cornu ammonis and the subiculum. This view is supported by histochemical findings in the tenrec (immunoreactivity to calcium binding proteins) as well as the rat (data taken from the literature). The HCt is therefore considered a region in its own right within the hippocampal formation. It may be tentatively correlated with the medial cortex of reptiles, while the dentate area and the cornu ammonis may have evolved de novo in mammals.
... The indusium griseum (IG) is a thin bilateral stripe-like allocortical brain area covering the entire anterior-posterior extent of the corpus callosum at the basis of the cingulate cortex. According to its topographical localization, the IG can be subdivided into an anterior part bending around the genu of the corpus callosum, a dorsal part overlying the corpus callosum surface, and a posterior part around the splenium of the corpus callosum, closely associated with the fasciola cinerea (FC) (Künzle, 2004). The long anterior-posterior expansion of this otherwise narrow structure implies proximity to several different brain areas. ...
... The latter, most common view is mainly based on similarities between IG and DG concerning cytoarchitecture, cell morphology, and neuronal projections (Wyss and Sripanidkulchai, 1983;Adamek et al., 1984;Laplante et al., 2013). Finally, it has also been suggested that the IG should be considered as a distinct subregion within the hippocampal formation (Künzle, 2004). The idea that the IG is more than a mere hippocampal rudiment is supported by a recent histological and magnetic resonance imaging study on the human IG clearly confirming that it does not show any signs of regression during postnatal development (Bobić Rasonja et al., 2019). ...
... There has been an ongoing debate on the classification of the IG, as morphological studies so far did not allow a clear assignment to any distinct brain structure. Künzle (2004) divided the IG of the hedgehoc tenrec into an anterior precallosal, dorsal supracallosal, and posterior postcallosal portion. This subdivision is also confirmed in our study in the mouse IG. ...
The indusium griseum (IG) is a cortical structure overlying the corpus callosum along its anterior–posterior extent. It has been classified either as a vestige of the hippocampus or as an extension of the dentate gyrus via the fasciola cinerea, but its attribution to a specific hippocampal subregion is still under debate. To specify the identity of IG neurons more precisely, we investigated the spatiotemporal expression of calbindin, secretagogin, Necab2, PCP4, and Prox1 in the postnatal mouse IG, fasciola cinerea, and hippocampus. We identified the calcium-binding protein Necab2 as a first reliable marker for the IG and fasciola cinerea throughout postnatal development into adulthood. In contrast, calbindin, secretagogin, and PCP4 were expressed each with a different individual time course during maturation, and at no time point, IG or fasciola cinerea principal neurons expressed Prox1, a transcription factor known to define dentate granule cell fate. Concordantly, in a transgenic mouse line expressing enhanced green fluorescent protein (eGFP) in dentate granule cells, neurons of IG and fasciola cinerea were eGFP-negative. Our findings preclude that IG neurons represent dentate granule cells, as earlier hypothesized, and strongly support the view that the IG is an own hippocampal subfield composed of a distinct neuronal population.
... Similarly, the relative strength of the entorhinal projections to the Tu as compared to the Acb is much less in rodents [36,59,60] than in non-rodent species [29,39,61]. It may also be noted that the hippocampal continuation, the only other striatal input region projecting exclusively to the tenrec's rostromedial Tu [28], is poorly represented in the rat compared to other mammals [62]. One may speculate that the dentato-tubercular neurons in the DtHi represent an extension of the HCt into the dentate gyrus and are only present in species showing a well differentiated HCt as e.g. in tenrecs and primates [62]. ...
... Unlike the dentate projection to the HCt the projection to the olfactory tubercle cannot be explained by a retrograde-anterograde collateral transport of tracer [28]. Tubercular terminations are not seen in the case with a BDA injection largely confined to the dentate molecular layer (Fig. 1C,1G), and tubercular projections are noted in the cases with dentate injections of WGA-HRP (Fig. 1B,1E,1F), a tracer substance not known to be transported in a retrograde-anterograde collateral fashion [40]. ...
... Wheat germ agglutinin conjugated to horseradish peroxidase (WGA-HRP; Sigma; n = 7) and biotinylated dextran amine (BDA; Sigma; n = 5) were used as tracer substances. Most cases have been described previously with regard to other connections [26,28,82]. The additional tracer injections (Et01-47W, Et03-58W) were done in the same fashion: The WGA-HRP (1.5–8 nl of a 2–5% solution in distilled water) was pressure injected through a glass micropipette (tip diameter 8–15 μm) attached to a Hamilton syringe driven by a micromanipulator. ...
The dentate gyrus is well known for its mossy fiber projection to the hippocampal field 3 (CA3) and its extensive associational and commissural connections. The dentate gyrus, on the other hand, has only few projections to the CA1 and the subiculum, and none have clearly been shown to extrahippocampal target regions.
Using anterograde and retrograde tracer techniques in the Madagascan lesser hedgehog tenrec (Afrosoricidae, Afrotheria) it was shown in this study that the dentate hilar region gave rise to a faint, but distinct, bilateral projection to the most rostromedial portion of the olfactory tubercle, particularly its molecular layer. Unlike the CA1 and the subiculum the dentate gyrus did not project to the accumbens nucleus. A control injection into the medial septum-diagonal band complex also retrogradely labeled cells in the dentate hilus, but these neurons were found immediately adjacent to the heavily labeled CA3, while the tracer injections into the rostromedial tubercle did not reveal any labeling in CA3.
The dentate hilar neurons projecting to the olfactory tubercle cannot be considered displaced cells of CA3 but represent true dentato-tubercular projection neurons. This projection supplements the subiculo-tubercular projection. Both terminal fields overlap among one another as well as with the fiber terminations arising in the anteromedial frontal cortex. The rostromedial olfactory tubercle might represent a distinct ventral striatal target area worth investigating in studies of the parallel processing of cortico-limbic information in tenrec as well as in cat and monkey.
... The cortical organization, neuronal morphology, neurochemistry, and patterns of afferent and efferent projections of the IG have been extensively studied in animal models (Abbie 1938(Abbie , 1939(Abbie , 1940Sturrock 1977Sturrock , 1978aSturrock , 1978bSturrock , 1978cWyss and Sripanidkulchai 1983;Adamek et al. 1984;Ino et al. 1987, Kunzle 2004, Jinno et al. 2007Laplante et al. 2013). The development of the IG and its neuronal and glial differentiation has also been quantitatively studied in the mouse brain (Sturrock 1977(Sturrock , 1978a(Sturrock , 1978b(Sturrock , 1978c. ...
... These data challenge the impression that may be gained from micro neuropil and complexity of the connectivity network within the IG. Moreover, these results show a pattern that is strikinly similar to the pattern of afferent and efferent projections in the adult rodent IG (Wyss and Sripanidkulchai 1983;Adamek et al. 1984;Kunzle 2004;Laplante et al. 2013). ...
To uncover the ontogenesis of the human indusium griseum (IG), 28 post-mortem fetal human brains, 12-40 postconceptional weeks (PCW) of age, and 4 adult brains were analyzed immunohistochemically and compared with post-mortem magnetic resonance imaging (MRI) of 28 fetal brains (14-41 PCW). The morphogenesis of the IG occurred between 12 and 15 PCW, transforming the bilateral IG primordia into a ribbon-like cortical lamina. The histogenetic transition of sub-laminated zones into the three-layered cortical organization occurred between 15 and 35 PCW, concomitantly with rapid cell differentiation that occurred from 18 to 28 PCW and the elaboration of neuronal connectivity during the entire second half of gestation. The increasing number of total cells and neurons in the IG at 25 and 35 PCW confirmed its continued differentiation throughout this period. High-field 3.0 T post-mortem MRI enabled visualization of the IG at the mid-fetal stage using T2-weighted sequences. In conclusion, the IG had a distinct histogenetic differentiation pattern than that of the neighboring intralimbic areas of the same ontogenetic origin, and did not show any signs of regression during the fetal period or postnatally, implying a functional role of the IG in the adult brain, which is yet to be disclosed.
... In all mammals, it consists of identical, similarly convoluted and interlocked 3-layered subdivisions, which from medial to lateral are the dentate gyrus (DG), the hippocampus proper or Ammon's horns ( cornu ammonis or CA fields 1-3), and the subiculum (Sub) [Witter and Amaral, 2004;Hevner, 2016]. It is rostrally continuous with a narrow strip of gray matter called indusium griseum , which is sometimes considered a hippocampal vestige [Künzle, 2004;Laplante et al., 2013]. For details on the structure, connections, and function of the HF, the readers are also referred to other articles of this special issue [for instance, see Fig. 1 in Witter et al.,this issue,. ...
... This previous proposal is also supported by the comparison with the avian medial pallium, showing the high similarity in terms of position and cytoarchitecture of reptilian MC and at least the avian ventral hippocampus. The fact that the latter expresses Prox1 is also a proof that a DG-like area was likely present in the medial pallium of stem amniotes [Abellán et al., 2014], instead of being a novel acquisition of mammals [Künzle, 2004;Striedter, 2016]. If confirmed that the MC of reptiles also expresses Prox1, this would also disagree with the proposal that this reptilian structure is comparable to the mammalian indusium griseum , as the latter does not express Prox1 [Abellán et al., 2014]. ...
The hippocampal formation is a highly conserved structure of the medial pallium that works in association with the entorhinal cortex, playing a key role in memory formation and spatial navigation. Although it has been described in several vertebrates, the presence of comparable subdivisions across species remained unclear. This panorama has started to change in recent years thanks to the identification of some of the genes that regulate the development of the hippocampal formation in the mouse and help to delineate its subdivisions based on molecular features. Some of these genes have been used to try to identify subdivisions in chicken and lizards comparable to those of the mammalian hippocampal formation and the entorhinal cortex. Here, we review some of these data, which suggest the existence of fields comparable to the dentate gyrus, CA3, CA1, subiculum, as well as medial and lateral parts of the entorhinal cortex in all amniotes. We also analyze available data suggesting the existence of serial connections between these fields, speculate on the possible existence of auto-associative loops in CA3, and discuss general principles governing the formation of the connections.
... In mammals, the hippocampal formation (HF) comprises three cytoarchitectonically distinct subdivisions, which from lateral to medial are: the subiculum, the hippocampus proper (Ammon's horn fields or cornu ammonis, subdivided in CA1, CA2, and CA3 fields) and the dentate gyrus (reviewed in Witter and Amaral, 2004;Witter, 2012). It also includes a rostral continuation called indusium griseum (Künzle, 2004). Within the HF, each subdivision is unique regarding its histological, neurochemical and connectivity patterns (Witter and Amaral, 2004;Witter, 2012). ...
... Comparison of the chicken, crocodile, and lizard hippocampal formation (Nissl images in Papp et al., 2007, for lizard and crocodile;Puelles et al., 2007, for chicken) points to the striking topological and cytoarchitectonic similarity of the chicken ventral hippocampus and the lizard/crocodile medial cortex, and the chicken V-shaped area (especially its dorsal part) to the lizard/crocodile dorsomedial cortex. Although some authors have suggested that the reptilian medial cortex is comparable to mammalian DG and the reptilian dorsomedial cortex is comparable to CA3 (Martínez-Guijarro et al., 1990), other authors suggested that the reptilian medial cortex is comparable to the mammalian indusium griseum (Künzle, 2004), or that both reptilian cortices maybe like mammalian CA3 (Papp et al., 2007). The possible common origin of DG and CA3 may explain why the connections of the avian V-shaped area and the reptilian medial/dorsomedial cortices are a mixture of those of mammalian DG and CA3 [reciprocal connections with the septum, and both ipsi-and contralateral (commissural) projections to other parts of the hippocampal formation; birds: (Casini et al., 1986;Atoji and Wild, 2004;Montagnese et al., 2004); for mammals see (Witter and Amaral, 2004); reptiles: (Lopez-Garcia and Martinez-Guijarro, 1988;Olucha et al., 1988;Martínez-Guijarro et al., 1990;Hoogland and Vermeulen-VanderZee, 1993)]. ...
We carried out a study of the expression patterns of seven developmental regulatory genes (Lef1, Lhx2, Lhx9, Lhx5, Lmo3, Lmo4, and Prox1), in combination with topological position, to identify the medial pallial derivatives, define its major subdivisions, and compare them between mouse and chicken. In both species, the medial pallium is defined as a pallial sector adjacent to the cortical hem and roof plate/choroid tela, showing moderate to strong ventricular zone expression of Lef1, Lhx2, and Lhx9, but not Lhx5. Based on this, the hippocampal formation (indusium griseum, dentate gyrus, Ammon's horn fields, and subiculum), the medial entorhinal cortex, and part of the amygdalo-hippocampal transition area of mouse appeared to derive from the medial pallium. In the chicken, based on the same position and gene expression profile, we propose that the hippocampus (including the V-shaped area), the parahippocampal area (including its caudolateral part), the entorhinal cortex, and the amygdalo-hippocampal transition area are medial pallial derivatives. Moreover, the combinatorial expression of Lef1, Prox1, Lmo4, and Lmo3 allowed the identification of dentate gyrus/CA3-like, CA1/subicular-like, and medial entorhinal-like comparable sectors in mouse and chicken, and point to the existence of mostly conserved molecular networks involved in hippocampal complex development. Notably, while the mouse medial entorhinal cortex derives from the medial pallium (similarly to the hippocampal formation, both being involved in spatial navigation and spatial memory), the lateral entorhinal cortex (involved in processing non-spatial, contextual information) appears to derive from a distinct dorsolateral caudal pallial sector.
... The function of the indusium griseum remains unclear. Tract-tracing studies indicate that, in rats and mice (Wyss and Sripanidkulchai, 1983;Adamek et al., 1984), and to a lesser extent in Madagascan hedgehogs (Kunzle, 2004), the indusium griseum receives direct projections from the main olfactory bulb. In hedgehogs, efferents of the indusium griseum reach, among other sites, the minor islands of Calleja (Kunzle, 2004). ...
... Tract-tracing studies indicate that, in rats and mice (Wyss and Sripanidkulchai, 1983;Adamek et al., 1984), and to a lesser extent in Madagascan hedgehogs (Kunzle, 2004), the indusium griseum receives direct projections from the main olfactory bulb. In hedgehogs, efferents of the indusium griseum reach, among other sites, the minor islands of Calleja (Kunzle, 2004). There is evidence that projections from the indusium griseum to the paraventricular nucleus are involved in the regulation of oxytocin release in rabbits (Woods et al., 1969). ...
African mole-rats provide a unique taxonomic group for investigating the evolution and neurobiology of sociality. The two species investigated here display extreme differences in social organization and reproductive strategy. Naked mole-rats (NMRs) live in colonies, dominated by a queen and her consorts; most members remain nonreproductive throughout life but cooperate in burrowing, foraging, and caring for pups, for which they are not biological parents (alloparenting). In contrast, Cape mole-rats (CMRs) are solitary and intolerant of conspecifics, except during fleeting seasonal copulation or minimal maternal behavior. Research on other mammals suggests that oxytocin receptors at various telencephalic sites regulate social recognition, monogamous pair bonding, and maternal/allomaternal behavior. Current paradigms in this field derive from monogamous and polygamous species of New World voles, which are evolutionarily remote from Old World mole-rats. The present findings indicate that NMRs exhibit a considerably greater level of oxytocin receptor (OTR) binding than CMRs in the: nucleus accumbens; indusium griseum; central, medial, and cortical amygdaloid nuclei; bed nucleus of the stria terminalis; and CA1 hippocampal subfield. In contrast, OTR binding in the piriform cortex is intense in CMRs but undetectable in NMRs. We speculate that the abundance of OTR binding and oxytocin-neurophysin-immunoreactive processes in the nucleus accumbens of NMRs reflects their sociality, alloparenting behavior, and potential for reproductive attachments. In contrast, the paucity of oxytocin and its receptors at this site in CMRs may reflect a paucity of prosocial behaviors. Whether similarities in OTR expression between eusocial mole-rats and monogamous voles are due to gene conservation or convergent evolution remains to be determined.
... Two out of the 40 animals were injected with both the WGA-HRP and BDA at different cortical locations (the letters W and B following the case numbers were used to indicate the tracer injected, WGA-HRP and BDA, respectively). Most cases with cortical injections have been described previously with regard to other connections [49,50,51,55]. The additional tracer injections were done in the same fashion: The WGA-HRP (1.5–20 nl of a 2–7% solution in distilled water) was pressure injected through a glass micropipette (tip diameter 8–15 Am) attached to a Hamilton syringe driven by a micromanipulator . ...
... 8F) was obtained particularly from the injections into the shoulder region and the adjacent dorsolateral hemisphere of zone 4 (S45,Table 2e); these injections, however, also labeled slightly the ventroposterior nucleus. The cases of the groups M45 and M23, on the other hand, were scarcely connected with these nuclei but labeled the thalamic regions located more medially and rostrally [50]. One of the most extensive cortico-striatal projection pattern was found in Et01-22W, an M23 case (Fig. 6;Table 2b) involving the CPu mirror-like on both sides. ...
In order to get insight into the striopallidal organization in mammals with little differentiated brain the striatum of the lesser hedgehog tenrec (Afrotheria) was characterized histochemically and analysed with regard to its cortical afferents using axonal tracer substances. The majority of neocortical cells projecting to the striatum were found bilaterally in the layers 2 and 3 of the frontal hemisphere; caudalwards the relative number of cells increased somewhat in the upper layer 5. There was a topographical organization as far as the allocortical projections appeared confined to the ventral striatum, and the efferents from hippocampal, posterior paleocortical, somatosensory and audiovisual areas were distributed in largely different striatal territories. Projections from the anterior frontal cortex, on the other hand, terminated extensively upon the caudate-putamen and also involved the nucleus accumbens and the olfactory tubercle. In the latter region the molecular layer was especially involved. The entorhinal cortex also projected heavily to the olfactory tubercle but unlike other species it scarcely involved the nucleus accumbens. The cortical fibers were distributed in a relatively homogenous fashion within their striatal territory and there was little evidence for patches of high density terminations. Islands of low density labeling, however, were noted occasionally in the caudate-putamen. These islands were partly similar in size as the patches of neuropil staining obtained with anti-calretinin and anti-substance P. There were also hints for the presence of a shell-like region in the nucleus accumbens stained with anti-dopamine transporter and NADPh-diaphorase. The classical striosome-matrix markers such as calbindin, acetylcholinesterase and enkephalin, however, failed to reveal any compartmental organization.
... Although there is currently an intense debate about the subdivisions that constitute the pallial region, their derivatives and boundaries (Abellán et al., 2014;Puelles, 2017Puelles, , 2021Desfilis et al., 2018;Medina et al., 2021), numerous studies have demonstrated similarities between the mammalian hippocampal formation (HF) and derivatives of the medial pallium (MP) in the rest of vertebrates [for review see Butler (2017)] speaking for the homology of these structures. Topologically, the mammalian HF is located in the mediodorsal area of the telencephalon, bordered rostrally by the indusium griseum and the dorsal tenia tecta (Wyss and Sripanidkulchai, 1983;Künzle, 2004;Laplante et al., 2013). In adults, this cortical structure is composed of a central region, that shows a characteristic C-shape organized in three layers and the parahippocampal region [for a review see Amaral and Lavenex (2009)]. ...
In all vertebrates, the most dorsal region of the telencephalon gives rise to the pallium, which in turn, is formed by at least four evolutionarily conserved histogenetic domains. Particularly in mammals, the medial pallium generates the hippocampal formation. Although this region is structurally different among amniotes, its functions, attributed to spatial memory and social behavior, as well as the specification of the histogenetic domain, appears to be conserved. Thus, the aim of the present study was to analyze this region by comparative analysis of the expression patterns of conserved markers in two vertebrate models: one anamniote, the amphibian Xenopus laevis ; and the other amniote, the turtle Trachemys scripta elegans , during development and in adulthood. Our results show that, the histogenetic specification of both models is comparable, despite significant cytoarchitectonic differences, in particular the layered cortical arrangement present in the turtle, not found in anurans. Two subdivisions were observed in the medial pallium of these species: a Prox1 + and another Er81/Lmo4 +, comparable to the dentate gyrus and the mammalian cornu ammonis region, respectively. The expression pattern of additional markers supports this subdivision, which together with its functional involvement in spatial memory tasks, provides evidence supporting the existence of a basic program in the specification and functionality of the medial pallium at the base of tetrapods. These results further suggest that the anatomical differences found in different vertebrates may be due to divergences and adaptations during evolution.
... These authors conclude that the indusium griseum and potentially also the taenia tecta might be phylogenetically old representations of the hippocampus. However, studies in the Madagascan hedgehog tenrec led to the conclusion that the indusium griseum, again showing a zinc-positive projection, might be correlated with lizard medial cortex, but that it is incorrectly considered a hippocampal homologue [Kunzle, 2004]. One would hope that more detailed functional studies on the lizard brain as well as on the taenia tecta and indusium griseum in mammals might clarify the validity of these claims. ...
The hippocampus in mammals is a morphologically well-defined structure, and so are its main subdivisions. To define the homologous structure in other vertebrate clades, using these morphological criteria has been difficult, if not impossible, since the typical mammalian morphology is absent. Although there seems to be consensus that the most medial part of the pallium represents the hippocampus in all vertebrates, there is no consensus on whether all mammalian hippocampal subdivisions are present in the derivatives of the medial pallium in all vertebrate groups. The aim of this paper is to explore the potential relevance of connections to define the hippocampus across vertebrates, with a focus on mammals, reptiles, and birds.
... Olfactory information is also processed in the orbitofrontal cortex and the insula as secondary olfactory cortices (Saive et al., 2014;Zelano and Sobel, 2005). Finally, the olfactory system is connected with the limbic system via the perforant pathway (Witter, 2007) and via the indiseum griseum (Adamek et al., 1984;Kunzle, 2004), which are the main neuronal ways to create olfactory learning and memory. ...
... Related fibers projecting to wide areas of the neocortex have also been shown (Gray, 1918), although no further anatomical studies on humans have so far been conducted to confirm these findings. More recent studies using axonal tracing techniques in hedgehogs have demonstrated efferent connections from the IG and LS to the subcallosal septum, the olfactory tubercle, and the island of Calleja (Kü nzle, 2004). There were also afferent connections from the entorhinal cortex (collaterals from neurons projecting to the dentate area), the anterior and posterior piriform cortices as well as the supramammillary region. ...
... Whereas the IG has the shape of a band, the AHC is more globular in appearance. While the functional roles of the IG and AHC are largely unknown, both structures share the same general laminar organization and a similar pattern of connectivity (Wyss and Sripanidkulchai, 1983;Kunzle, 2004), the only difference thus far reported is a modest projection to the olfactory bulb arising from the AHC but not the IG (de Olmos et al., 1978;Wyss and Sripanidkulchai, 1983;Shipley et al., 2004). The IG and AHC have also been suggested to be extensions or continuations of the hippocampal formation (Smith, 1897;Wyss and Sripanidkulchai, 1983), due to their general structural similarities. ...
The indusium griseum (IG) and anterior hippocampal continuation (AHC) are longitudinal and continuous structures that consist of two narrow strips of gray matter overlying the rostrocaudal length of the corpus callosum, extending rostrally to the genu of the corpus callosum and ventrally to the rostrum. The present study aimed to characterize the phenotype of neuronal innervations to the IG-AHC and their intra-structural topographic organization. Using immunohistochemistry, we found nerve fibres expressing choline acetyltransferase, tyrosine hydroxylase, dopamine-β-hydroxylase, the serotonin reuptake transporter as well as glutamic acid decarboxylase-67 and parvalbumin. These suggest that the IG and AHC are innervated by acetylcholine, dopamine, noradrenaline, 5-hydroxytryptamine and GABA neurons. More importantly, all these fibres display a topographic laminar distribution in both brain areas. The presence of varicosities along the nerve fibres suggests that these neurotransmitters are released extracellullarly to exert a physiological action. Finally, the structural similarities with the dentate gyrus support the idea that the IG and AHC are anatomically associated, if not continuous, with this area and may represent in mammals a vestige of the hippocampus.
... SHi is known to be involved in nonspatial associative learning by integrating external sensory inputs with self-motivation stimuli (Vertes and Kocsis, 1997). Neurons in SHi receive inputs from the OB and anterior thalamic nuclei (Wyss and Sripanidkulchai, 1983;Kunzle, 2004) where phactr2 mRNA was highly expressed, suggesting that these limbic networks are molecularly specified by the expression of Phactr2. ...
Phosphatase and actin regulators (Phactrs) are a novel family of proteins expressed in the brain, and they exhibit both strong modulatory activity of protein phosphatase 1 and actin-binding activity. Phactrs are comprised of four family members (Phactr1-4), but their detailed expression patterns during embryonic and postnatal development are not well understood. We found that these family members exhibit different spatiotemporal mRNA expression patterns. Phactr4 mRNA was found in neural stem cells in the developing and adult brains, whereas Phactr1 and 3 appeared to be expressed in post-mitotic neurons. Following traumatic brain injury which promotes neurogenesis in the neurogenic region and gliogenesis in the injury penumbra, the mRNA expression of phactr2 and 4 was progressively increased in the injury penumbra, and phactr4 mRNA and protein induction was observed in reactive astrocytes. These differential expression patterns of phactrs imply specific functions for each protein during development, and the importance of Phactr4 in the reactive gliosis following brain injury.
... Some fibers also originate in the olfactory bulb and dentate gyrus. Additional efferents are directed to subcallosal septo-hippocampal nucleus, olfactory tubercle and the islands of Calleja [17]. Anyway, further investigations using modern tracing techniques which selectively follow axons will clarify exact origin of fibers longitudinal strae contain. ...
Two pairs of sagittal longitudinal striae, medial and lateral, are slender bundles of fibers located on the dorsal surface of corpus callosum, situated deeply in the longitudinal fissure of telencephalon. Imbedded in the structure of tiny gyrus, indusium griseum, they are, in fact, supracallosal fibers of the fornix, previously called fornix longus.
Longitudinal striae were investigated in 25 fixed human brains obtained from autopsies. Macrodissection and morphometric methods were used in order to find out and analyze the appearance and gross morphological variability of longitudinal striae, as well as their inter-individual relations.
Lateral longitudinal striae were located along the sulci of corpus callosum. Medial striae were positioned along the sagittal midline and they were mostly individual. However, they were at times connected, spanned or duplicated. Longitudinal striae make a characteristic pattern on the dorsal surface of corpus callosum. A classification of striae is made on the basis of their appearance.
Although similar at first sight the striae, especially medial ones, have some individual features which make the pattern variable. Medial striae are more variable than the lateral ones. Perhaps functional neuroimaging and DT MRI will disclose the enigma of these striae.
... Beta-gal mRNA is expressed in PTPH1-KO cerebellum, cortex, hippocampus and substriatal regions (midbrain, thalamic nuclei, pontine region); no beta-gal expression detected in WT brain extracts (first lane of each block); histone H2A gene was used as positive control (second lane). receiving afferents from the entorhinal and pyriform cortex and projecting to the septohippocampal nuclei, olfactory tubercle (presumably the tenia tecta) and the medial frontal cortex [53,54]. The expression of PTPH1 in these specific regions suggests a potential role in the processing/ integration of memory and sensory information to the SHi and likely the cortex. ...
The present study has investigated the protein tyrosine phosphatase H1 (PTPH1) expression pattern in mouse brain and its impact on CNS functions.
We have previously described a PTPH1-KO mouse, generated by replacing the PTP catalytic and the PDZ domain with a LacZ neomycin cassette. PTPH1 expression pattern was evaluated by LacZ staining in the brain and PTPH1-KO and WT mice (n = 10 per gender per genotype) were also behaviorally tested for CNS functions.
In CNS, PTPH1 is expressed during development and in adulthood and mainly localized in hippocampus, thalamus, cortex and cerebellum neurons. The behavioral tests performed on the PTPH1-KO mice showed an impact on working memory in male mice and an impaired learning performance at rotarod in females.
These results demonstrate for the first time a neuronal expression of PTPH1 and its functionality at the level of cognition.
... Additional neurons in the molecular and polymorph layer have been described as well (Wouterlood 1981;ten Donkelaar 2000). Note that in several mammalian species, the anterior (supracallosal) continuation of the hippocampus, indusium griseum, and tenia tecta (considered the olfactory hippocampus) shows similarities to the lizard medial cortex, where the dentate and CA fields form a continuous sheet of cells with two morphologies, granule and pyramidal (Stephan 1975;Wyss and Sripanidkulchai 1983;Shipley and Adamek 1984;Künzle 2004). Projections distribute widely in the cortex, including a return projection to the small-celled part. ...
Comparative neuroanatomy suggests that the CA3 region of the mammalian hippocampus is directly homologous with the medio-dorsal pallium in birds and reptiles, with which it largely shares the basic organization of primitive cortex. Autoassociative memory models, which are generically applicable to cortical networks, then help assess how well CA3 may process information and what the crucial hurdles are that it may face. The analysis of such models points at spatial memories as posing a special challenge, both in terms of the attractor dynamics they can induce and how they may be established. Addressing such a challenge may have favored the evolution of elements of hippocampal organization observed only in mammals.
... Using the definition of the DG as provided here, and in line with many other authors, it seems thus safe to conclude that the small and large cell portions of the reptilian cortex do correspond to the dentate and CA area, respectively , as seen in mammals, although the reptiles have only a single CA field. In fact, in several mammals, such as the opossum, mice, rat and tenrec, parts of the hippocampus, generally referred to as the anterior tenia tecta and indusium griseum, resemble the lizard medial cortex, where the dentate and CA fields form a continuous sheet of cells with two morphologies, granule and pyramidal (Stephan, 1975; Wyss and Sripanidkulchai, 1983; Shipley and Adamek, 1984; Gloor, 1997; Künzle, 2004 ). A further piece of information supporting this conclusion is that, similar to what has been reported in the mammalian DG, the medial cortex of adult lizards exhibits neurogenesis during the lifespan and differentiated neurons actually give rise to zinccontaining projections to other parts of the cortex, thus resulting in a continuous growth of it. ...
In the mammalian hippocampus, the dentate gyrus (DG) is characterized by sparse and powerful unidirectional projections to CA3 pyramidal cells, the so-called mossy fibers (MF). The MF form a distinct type of synapses, rich in zinc, that appear to duplicate, in terms of the information they convey, what CA3 cells already receive from entorhinal cortex layer II cells, which project both to the DG and to CA3. Computational models have hypothesized that the function of the MF is to enforce a new, well-separated pattern of activity onto CA3 cells, to represent a new memory, prevailing over the interference produced by the traces of older memories already stored on CA3 recurrent collateral connections. Although behavioral observations support the notion that the MF are crucial for decorrelating new memory representations from previous ones, a number of findings require that this view be reassessed and articulated more precisely in the spatial and temporal domains. First, neurophysiological recordings indicate that the very sparse dentate activity is concentrated on cells that display multiple but disorderly place fields, unlike both the single fields typical of CA3 and the multiple regular grid-aligned fields of medial entorhinal cortex. Second, neurogenesis is found to occur in the adult DG, leading to new cells that are functionally added to the existing circuitry, and may account for much of its ongoing activity. Third, a comparative analysis suggests that only mammals have evolved a DG, despite some of its features being present also in reptiles, whereas the avian hippocampus seems to have taken a different evolutionary path. Thus, we need to understand both how the mammalian dentate operates, in space and time, and whether evolution, in other vertebrate lineages, has offered alternative solutions to the same computational problems.
... The significant reduction in the number of SRIH hilar cells after the Aβ administration reported here is in keeping with recent in vitro data (Geci et al., 2007). Although we did not inject Aβ directly into the hippocampus, Aβ might exert their effects in distant targets of the application site as it has been reported (Sigurdsson et al., 1997;Stepanichev et al., 2000), inducing for example a neural disconnection between some neuronal structures (Ahmed et al., 1995;Kunzle, 2004). Disconnection of DG from the entorhinal cortex, its major input, is observed in early stages of AD (Ohm, 2007). ...
We examined the potential protective effect of BDNF against beta-amyloid-induced neurotoxicity in vitro and in vivo in rats. In neuronal cultures, BDNF had specific and dose-response protective effects on neuronal toxicity induced by Abeta(1-42) and Abeta(25-35). It completely reversed the toxic action induced by Abeta(1-42) and partially that induced by Abeta(25-35). These effects involved TrkB receptor activation since they were inhibited by K252a. Catalytic BDNF receptors (TrkB.FL) were localized in vitro in cortical neurons (mRNA and protein). In in vivo experiments, Abeta(25-35) was administered into the indusium griseum or the third ventricle and several parameters were measured 7 days later to evaluate potential Abeta(25-35)/BDNF interactions, i.e. local measurement of BDNF release, number of hippocampal hilar cells expressing SRIH mRNA and assessment of the corpus callosum damage (morphological examination, pyknotic nuclei counting and axon labeling with anti-MBP antibody). We conclude that BDNF possesses neuroprotective properties against toxic effects of Abeta peptides.
The peak-interval (PI) procedure is a temporal discrimination task used with animals, significantly affected by the hippocampus and the striatum. We focused on N-methyl-D-aspartate (NMDA) receptors because they are found at high concentrations in the hippocampus, and investigated the effects of D, L-2-amino-5-phosphonopentanoic acid (AP5), an NMDA receptor antagonist, in the PI procedure. Rats were given acute administrations of AP5 into indusium griseum after PI training for 30 s. The result indicated that AP5 induced a rightward response distribution shift suggesting that AP5 produced an overestimation of the criterion time. This finding implies that NMDA receptors surrounding indusium griseum affect the PI procedure’s timing behavior, which indicates NMDA receptors’ role in time perception.
The presence of substance P (SP) receptor (Neurokinin-1 receptor, NK1R) in the indusium griseum (IG) and anterior hippocampal continuation (AHC) during postnatal development was studied by immunocytochemistry (ICC). NK1R-immunopositive neurons (NK1RIP-n) first appeared in both areas on postnatal day (P) 5. From P5 onward, their distribution pattern was adult-like. In sagittal sections NK1RIP-n formed a narrow strip of neurons and dendrites that were located over the corpus callosum (cc); in coronal sections they were found in a roughly triangular area at the base of the cingulate cortex (Cg) on the dorsal surface of the cc. NK1RIP-n were also found in the AHC, which is considered as a subcallosal extension of the IG, located ventral to the genu of the cc. At all ages studied, IG NK1RIP-n sent dendrites to the contralateral IG, the underlying cc, and the Cg. Moreover, NK1RIP-n located in the Cg and the cc sent dendrites to the IG. The present findings are in line with previous ICC studies describing dopaminergic and serotoninergic afferents to the IG. Together these data suggest that, through NK1R, SP could play an important role in regulating the release mechanisms of these afferents and that it could be an important developmental factor. Notably, IG neurons could be activated by cortical and intracallosal afferents.
Connections between the left and right brain hemispheres, known as commissures, are essential for coordinating everyday sensory-motor and cognitive functions. Across vertebrates, telencephalic commissures share a similar organization, likely due to highly conserved events of early brain development. However, lineage-specific novelties in commissural systems have also occurred, including axonal rerouting through preexistent tracts, and the origin and expansion of new tracts, such as the corpus callosum. This chapter discusses the phylogenetic history of telencephalic commissures, the possible developmental scenarios involved in the evolution of commissural innovations, and the potential applications of an evolutionary developmental approach to human brain research.
The somatosensory fMRI response to electrical stimulation of the middle phalange of the second digit of four rats at a spatial resolution of 200 micron cubic at 9.4 T is reported. At high threshold (P < 0.002), activated voxels encompass a penetrating vein that passes across gray matter. These voxels lie mostly in three contiguous slices perpendicular to the pial surface. This activation is assigned to the representation in the forepaw barrel subfield (FBS) of a single cortical column of this phalange. In addition, activation of the Indusium Grieseum (IG) is visualized robustly. Voxels revealed by fMRI were used to observe functional connectivity to other voxels of the sensorimotor cortex using fcMRI. Results of this experiment were analyzed as a function of decreasing threshold, which exhibited spreading connectivity that revealed S2, M1/M2 and contralateral S1. Noting that every cubic mm of tissue contains 125 voxels, connectivity patterns are complex. It is hypothesized that they reflect connections within gray matter by association fibers. S2 and IG revealed connectivities with many voxels across the sensorimotor cortex. These regions also showed sub-regional variation of connectivity. A 1 cm diameter surface coil with a local low-noise rf amplifier was used in these studies. The usual region of sensitivity (ROS) of such a coil is 1 cm diameter by 0.5 cm depth. Significant connectivity was observed between time courses of voxels that were within the ROS and voxels that were outside, which extends the volume of tissue that can be observed by the methods of this paper.
Cathepsin C (CC) (EC 3.4.14.1, dipeptidyl peptidase I) is a lysosomal cysteine protease that is required for the activation of several granule-associated serine proteases in vivo. CC has been shown to be constitutively expressed in various tissues, but the enzyme is hardly detectable in central nervous system (CNS) tissues. In the present study, we investigated the regional and cellular distribution of CC in normal, aging and pathological mouse brains. Immunoblotting failed to detect CC protein in whole brain tissues of normal mice, as previously described. However, low proteolytic activity of CC was detected in a brain region-dependent manner, and granular immunohistochemical signals were found in neuronal perikarya of particular brain regions, including the accessory olfactory bulb, the septum, CA2 of the hippocampus, a part of the cerebral cortex, the medial geniculate, and the inferior colliculus. In aged mice, the number of CC-positive neurons increased to some extent. The protein level of CC and its proteolytic activity showed significant increases in particular brain regions of mouse models with pathological conditions - the thalamus in cathepsin D-deficient mice, the hippocampus of ipsilateral brain hemispheres after hypoxic-ischemic brain injury, and peri-damaged portions of brains after penetrating injury. In such pathological conditions, the majority of the cells that were strongly immunopositive for CC were activated microglia. These lines of evidence suggest that CC is involved in normal neuronal function in certain brain regions, and also participates in inflammatory processes accompanying pathogenesis in the CNS.
The present study analyses the overall extrinsic connectivity of the non-olfactory amygdala (Ay) in the lesser hedgehog tenrec. The data were obtained from tracer injections into the lateral and intermediate portions of the Ay as well as several non-amygdalar brain regions. Both the solitary and the parabrachial nucleus receive descending projections from the central nucleus of the Ay, but only the parabrachial nucleus appears to project to the Ay. There is one prominent region in the ventromedial hypothalamus connected reciprocally with the medial and central Ay. Amygdalar afferents clearly arise from the dorsomedial thalamus, the subparafascicular nuclei and the medial geniculate complex (GM). Similar to other subprimate species, the latter projections originate in the dorsal and most caudal geniculate portions and terminate in the dorsolateral Ay. Unusual is the presence of amygdalo-projecting cells in the marginal geniculate zone and their virtual absence in the medial GM. As in other species, amygdalo-striatal projections mainly originate in the basolateral Ay and terminate predominantly in the ventral striatum. Given the poor differentiation of the tenrec's neocortex, there is a remarkable similarity with regard to the amygdalo-cortical connectivity between tenrec and rat, particularly as to prefrontal, limbic and somatosensorimotor areas as well as the rhinal cortex throughout its length. The tenrec's isocortex dorsomedial to the caudal rhinal cortex, on the other hand, may not be connected with the Ay. An absence of such connections is expected for primary auditory and visual fields, but it is unusual for their secondary fields.
The hedgehog tenrec (Afrosoricidae) has a very poorly differentiated neocortex. Previously its primary sensory regions have been characterized with hodological and electrophysiological techniques. Unlike the marsupial opossum the tenrec may also have a separate motor area as far as there are cortico-spinal cells located rostral to the primary somatosensory cortex. However, not knowing its thalamic input it may be premature to correlate this area with the true (mirror-image-like) primary motor cortex in higher mammals. For this reason the tenrec's thalamo-cortical connections were studied following tracer injections into various neocortical regions. The main sensory areas were confirmed by their afferents from the principal thalamic nuclei. The dorsal lateral geniculate nucleus, in addition, was connected with the retrosplenial area and a rostromedial visual region. Unlike the somatosensory cortex the presumed motor area did not receive afferents from the ventrobasal thalamus but fibers from the cerebello-thalamic target regions. These projections, however, were not restricted to the motor area, but involved the entire somatosensorimotor field as well as adjacent regions. The projections appeared similar to those arising in the rat thalamic ventromedial nucleus known to have a supporting function rather than a specific motor task. The question was raised whether the input from the basal ganglia might play a crucial role in the evolution of the mammalian motor cortex? Certainly, in the tenrec, the poor differentiation of the motor cortex coincides with the virtual absence of an entopeduncular projection to the ventrolateral thalamus.
Unlike the basal ganglia input from the midline and intralaminar nuclei, the origin and prominence of striatal projections arising in the lateral thalamus varies considerably among mammals being most restricted in the opossum and monkey, most extensive in the rat. To get further insight into the evolution of thalamo-striatal pathways the Madagascar lesser hedgehog tenrec (Afrotheria) was investigated using anterograde and retrograde flow techniques. An extensive medial thalamic region (including presumed equivalents to the paraventricular, parataenial and dorsomedial nuclei as well as the reuniens complex), the rostral (central) and caudal (parafascicular) intralaminar nuclei were shown to give rise to striatal projections. Additional projections originated in the ventral anterolateral nuclear group and regions within and around the medial geniculate complex. Similar to the rat there was also substantial projections from the lateral posterior-pulvinar complex and the ventral posterior nucleus. The fibers terminated extensively across the striatum in a mainly homogeneous fashion. Isolated patches of low-density terminations were found in the caudoputamen. This inhomogeneous labeling pattern appeared similar to one described in the cat with the unlabeled islands showing features of striosomes. The medial and intralaminar nuclei also projected heavily upon the olfactory tubercle. Differential innervation patterns were noted in the polymorphous layer, the deep and the superficial molecular layer.
The neuropeptides oxytocin and vasopressin and their receptors have been implicated in elements of mammalian social behavior such as attachment to mates and offspring, but their potential role in mediating other types of social relationships remains largely unknown. We performed receptor autoradiography to assess whether forebrain oxytocin receptor (OTR) or vasopressin V1a receptor (V1aR) distributions differed with social structure in two closely related and ecologically similar species of South American rodents, the colonial tuco-tuco (Ctenomys sociabilis) and the Patagonian tuco-tuco (Ctenomys haigi). Long-term field studies have revealed that C. haigi is solitary, whereas C. sociabilis is social and provides a model of female-based group living. Our analyses revealed marked differences in OTR and V1aR distributions between these species. For example, only C. sociabilis had OTR binding in the piriform cortex and thalamus and V1aR binding in the olfactory bulbs. In contrast, C. haigi exhibited dramatically higher levels of OTR binding throughout the lateral septum and hippocampus. More generally, the group-living C. sociabilis exhibited a pattern of nucleus accumbens OTR and ventral pallidum V1aR binding different from that associated with the formation of opposite-sex pair bonds in microtine rodents. Higher binding in the central nucleus of the amygdala of C. sociabilis was consistent with the hypothesis that formation of social groups in C. sociabilis may be facilitated by reduced social anxiety. Low OTR binding in the lateral septum might also be a permissive factor for group living in C. sociabilis. Future studies will expand on these analyses to explore interspecific differences in ctenomyid receptor binding patterns in a phylogenetic context.
Although there are remarkable differences regarding the output organization of basal ganglia between mammals and non-mammals, mammalian species with poorly differentiated brain have scarcely been investigated in this respect. The aim of the present study was to identify the pallidal neurons giving rise to thalamic projections in the Madagascar lesser hedgehog tenrec (Afrotheria). Following tracer injections into the thalamus, retrogradely labelled neurons were found in the depth of the olfactory tubercle (particularly the hilus of the Callejal islands and the insula magna), in subdivisions of the diagonal band complex, the peripeduncular region and the thalamic reticular nucleus. No labelled cells were seen in the globus pallidus. Pallidal neurons were tentatively identified on the basis of their striatal afferents revealed hodologically using anterograde axonal tracer substances and immunohistochemically with antibodies against enkephalin and substance P. The data showed that the tenrec's medial thalamus received prominent projections from ventral pallidal cells as well as from a few neurons within and ventral to the cerebral peduncle. The only regions projecting to the lateral thalamus appeared to be the thalamic reticular nucleus (RTh) and the dorsal peripeduncular nucleus (PpD). On the basis of immunohistochemical data and the topography of its thalamic projections, the PpD was considered to be an equivalent to the pregeniculate nucleus in other mammals. There was no evidence of entopeduncular (internal pallidal) neurons being present within the RTh/PpD complex, neuropils of which did not stain for enkephalin and substance P. The ventrolateral portion of RTh, the only region eventually receiving a striatal input, projected to the caudolateral rather than the rostrolateral thalamus. Thus, the striatopallidal output organization in the tenrec appeared similar, in many respects, to the output organization in non-mammals. This paper considers the failure to identify entopeduncular neurons projecting to the rostrolateral thalamus in a mammal with a little differentiated cerebral cortex, and also stresses the discrepancy between this absence and the presence of a distinct external pallidal segment (globus pallidus).
Detailed description of the brain size, rhinencephalon and hippocampal formation of the Bactrian camel is presented in our study. The brain weight of the Bactrian camel is 626 g averagely, and the encephalization quotient (EQ) value 1.3, indicating a high level of intelligence. The rhinencephalon is mature and well developed, accordant with the good olfactory sense. The hippocampus is relatively large, concomitant with the good ability of spatial memory. These anatomical features agree with the corresponding adaptive behaviors of the Bactrian camel and provide a morphological evidence of the camel to adapt to the acrid and semi- acrid environment.
The hippocampus consists of distinct anatomic regions that have been demonstrated to have different biological functions. To explore the molecular differences between hippocampal subregions, we performed transcriptional profiling analysis by using DNA microarray technology. The cRNA derived from the CA1, CA3, and dentate gyrus regions of the hippocampus and from spinal cord was hybridized to Affymetrix high-density oligo arrays. This systematic approach revealed sets of genes that were expressed specifically in subregions of the hippocampus corresponding to predefined cytoarchitectural boundaries, which could be confirmed by in situ hybridization and Real Time quantitative polymerase chain reaction. The relative enrichment and absence of genes in the hippocampal subregions support the conclusion that there is a molecular basis for the previously defined anatomic subregions of the hippocampus and also reveal genes that could be important in defining the unique functions of the hippocampal subfields. J. Comp. Neurol. 441:187–196, 2001. © 2001 Wiley-Liss, Inc.
Homologies between vertebrate forebrain subdivisions are still uncertain. In particular the identification of homologs of the mammalian neocortex or the dorsal ventricular ridge (DVR) of birds and reptiles is still a matter of dispute. To get insight about the organization of the primordia of the main telencephalic subdivisions along the anteroposterior axis of the neural tube, a fate map of the dorsal prosencephalon was obtained in avian chimeras at the 8- to 9-somite stage. At this stage, the primordia of the pallium, DVR and striatum were located on the dorsal aspect of the prosencephalon and ordered caudorostrally along the longitudinal axis of the brain. Expression of homeobox-containing genes of the Emx, Dlx and Pax families were used as markers of anteroposterior developmental subdivisions of the forebrain in mouse, chick, turtle and frog. Their expression domains delineated three main telencephalic subdivisions in all species at the onset of neurogenesis: the pallial, intermediate and striatal neuroepithelial domains. The fate of the intermediate subdivisions diverged, however, between species at later stages of development. Homologies between forebrain subdivisions are proposed based on the conservation and divergence of these gene expression patterns.
The distribution of the alpha subspecies of protein kinase C (PKC) in rat brain was demonstrated immunocytochemically by using polyclonal antibodies raised against a synthetic oligopeptide corresponding to the carboxyl-terminal sequence of alpha-PKC. The alpha-PKC-specific immunoreactivity was widely but discretely distributed in both gray and white matter. The immunoreactivity was associated predominantly with neurons, particularly with perikaryon, dendrite, or axon, but little was seen in the nucleus. Glial cells expressed this PKC subspecies poorly, if at all. The highest density of immunoreactivity was seen in the olfactory bulb, septohippocampal nucleus, indusium griseum, islands of Calleja, intermediate part of the lateral septal nucleus, and Ammon's horn. A moderately high density of the immunoreactivity was seen in the anterior olfactory nucleus, anterior commissure, cingulate cortex, dentate gyrus, compact part of the substantia nigra, interpeduncular nucleus, inferior olive, and olivocerebellar tract. This distribution pattern was consistent with that obtained by in situ hybridization histochemistry. The distribution of alpha-PKC immunoreactivity was different from that of beta I-, beta II-, and gamma-PKC immunoreactivity. These findings suggest that alpha-PKC is involved heavily in the control of specific functions of some restricted neurons.
Hippocampal area CA1 provides the major cortical output of the hippocampus, but only its projections to the subiculum and lateral septal nucleus are well characterized. The present study reexamines these extrinsic projections by using anterograde and retrograde tracing techniques. Injections of the anterograde tracer Phaseolus vulgaris leucoagglutinin (PHA-L) in the septal one-third of CA1 label axons and terminals in subicular, postsubicular, retrosplenial, perirhinal, and entorhinal cortices, lateral septal nucleus, and diagonal band of Broca. The septal CA1 injections also label terminal fields in contralateral CA1, and in contralateral subicular, postsubicular, perirhinal, and entorhinal cortices. Injections into the splenial one-third of CA1 label axons and terminals in subiculum, postsubiculum, ventral area infraradiata, and lateral septal nucleus, but they do not label axons and terminals on the contralateral side of the brain. Injections in the temporal one-third of CA1 label axons and terminals in subicular, parasubicular, entorhinal, and infraradiata cortices, anterior olfactory nucleus, olfactory bulb, lateral septal nucleus, nucleus accumbens, amygdala, and hypothalamus. The temporal CA1 injections label no axons on the contralateral side of the brain. These data demonstrate that CA1 has more widespread projections than previously appreciated, and they provide the first clear evidence that CA1 projects to the contralateral cortex and to the ipsilateral olfactory bulb, amygdala, and hypothalamus. The results also demonstrate a heterogeneity in the efferent projections originating in different septotemporal levels of CA1.
On the basis of stimulation studies, it has been proposed that the infralimbic cortex (ILC), Brodmann area 25, may serve as an autonomic motor cortex. To explore this hypothesis, we have combined anterograde tracing with Phaseolus vulgaris leucoagglutinin (PHA-L) and retrograde tracing with wheat germ aggutinin conjugated to horseradish peroxidase (WGA-HRP) to determine the efferent projections from the ILC. Axons exit the ILC in one of three efferent pathways. The dorsal pathway ascends through layers III and V to innervate the prelimbic and anterior cingulate cortices. The lateral pathway courses through the nucleus accumbens to innervate the insular cortex, the perirhinal cortex, and parts of the piriform cortex. In addition, some fibers from the lateral pathway enter the corticospinal tract. The ventral pathway is by far the largest and innervates the thalamus (including the paraventricular nucleus of the thalamus, the border zone between the paraventricular and medial dorsal nuclei, and the paratenial, reuniens, ventromedial, parafasicular, and subparafasicular nuclei), the hypothalamus (including the lateral hypothalamic and medial preoptic areas, and the suprachiasmatic, dorsomedial, and supramammillary nuclei), the amygdala (including the central, medial, and basomedial nuclei, and the periamygdaloid cortex) and the bed nucleus of the stria terminalis. The ventral efferent pathway also provides descending projections to autonomic cell groups of the brainstem and spinal cord including the periaqueductal gray matter, the parabrachial nucleus, the nucleus of the solitary tract, the dorsal motor vagal nucleus, the nucleus ambiguus, and the ventrolateral medulla, as well as lamina I and the intermediolateral column of the spinal cord. The ILC has extensive projections to central autonomic nuclei that may subserve a role in modulating visceral responses to emotional stimuli, such as stress.
The avian hippocampal formation (HP) is considered to be homologous to the mammalian hippocampus on the basis of topography, developmental origin and its role in processing spatial memory. However, the morphological organization of the avian HP is very different from that of mammals and components similar to the subdivisions of the mammalian structure are not readily recognizable. In passerine birds, three spatially and morphologically distinct populations of Calbindin immunoreactive neurones are found in the dorsolateral (DL), dorsomedial (DM) and ventral (V) aspects of HP. Iontophoresis of Phaseolus vulgar is leucoagglutinin revealed three consistently different projection patterns arising from the different subregions. Generally, there is a medial-to-lateral topographical organization of efferents in relation to the septal complex. The DL region could be paralleled to the subiculum of mammals with its main projections to the basal ganglia, the limbic archistriatum, the lateral septum and the paraxial meso-diencephalic centres. The 'V' subdivision is likely to be homologous to the Ammon's horn of mammals with its commissural projections to the contralateral HP. Based on its purely intrinsic connectivity, the DM region could be a good candidate for an equivalent of the dentate gyrus. Nitric oxide synthase (NOS) containing neural structures display a specific distribution within the hippocampal subregions which is uniform in all passerine species studied. However, there is a marked difference in the level of diffuse neuropil reactivity between food-storers versus non-storers. Unlike the mammalian homologue, avian hippocampal NOS positive neurones do not show a near complete co-localization with the inhibitory transmitter GABA.
There is now compelling evidence, based on studies in many species and laboratories, that cingulate cortex is one of the important targets of the hippocampal formation. Source structures include the hippocampus, subicular complex, and entorhinal cortex. Using new anatomical tract tracing techniques, several reports published in the late 1970s added considerably to our understanding of hippocampal formation outputs and showed that several tenets of hippocampal organization required revision. For years, the principal hippocampal outputs were regarded as subcortical projections via the fornix system. The subiculum, though well described by Lorente de Nó using the Golgi technique (Lorente de Nó, 1933), was usually ignored.
Reptiles and mammals are the two groups of vertebrates with well-developed cerebral cortices. Ray-finned fishes have forebrains that develop by an eversion of the rostral neural tube that reduces the roof of the telencephalon to a thin membrane (Nieuwenhuys, 1982; Northcutt and Davis, 1983). They have olfactory cortices on the ventrolateral walls of their cerebral hemispheres (e.g., Braford and Northcutt, 1974), but the eversion process seemingly precludes the formation of a cortical roof to the telencephalon. Cartilaginous fishes (such as sharks), fleshy-finned fishes (lungfishes and coelacanths), amphibians, reptiles, birds, and mammals all have forebrains that develop via a fundamentally different process. This involves an evagination of the rostral neural tube resulting in paired lateral ventricles, interventricular foramina, and a neuronal roof to the telencephalon that can form an extensive cerebral cortex. However, the telencephalic roof of sharks forms a solid mass of neurons lacking the lamination usually associated with the cerebral cortex (Smeets et al., 1983). Although amphibians (Northcutt and Kicliter, 1980) and lungfishes (Northcutt, 1986) have laminated cortices, they show little migration of neurons away from the ependyma. Birds have a small cerebral cortex, ostensibly resulting from a secondary reduction of the reptilian pattern (Benowitz, 1980). It is only in reptiles and mammals that the telencephalic roof develops into extensive and multilayered cortices.
The Madagascan lesser hedgehog tenrec was investigated to get insight into the areal evolution of the hippocampal formation in mammals with poorly differentiated brains. The hippocampal subdivisions were analyzed using cyto- and chemoarchitectural criteria; long associational and commissural connections were demonstrated with tracer techniques. The hedgehog tenrec shows a well differentiated dentate gyrus, CA3 and CA1. Their major intrinsic connections lie within the band of variations known from other species. The dentate hilar region shows calretinin-positive mossy cells with extensive projections to the molecular layer. The calbindin- and enkephalin-positive granule mossy fibers form a distinct endbulb and do not invade the CA1 as reported in the erinaceous hedgehog. Isolated granule cells with basal dendrites were also noted. A CA2 region is hard to identify architecturally; its presence is suggested due to its contralateral connections. Subicular and perisubicular regions are clearly present along the dorsal aspects of the hemisphere, but we failed to identify them unequivocally along the caudal and ventral tip of the hippocampus. A temporal portion of the subiculum, if present, differs in its chemoarchitecture from its dorsal counterpart. The perisubicular region, located medially adjacent to the dorsal subiculum may be equivalent to the rat's presubiculum; evidence for the presence of a parasubiculum was rather weak.
The projections of the septum of the lizard Podarcis hispanica (Lacertidae) were studied by combining retrograde and anterograde neuroanatomical tracing. The results confirm the classification of septal nuclei into three main divisions. The nuclei composing the central septal division (anterior, lateral, medial, dorsolateral, and ventrolateral nuclei) displayed differential projections to the basal telencephalon, preoptic and anterior hypothalamus, lateral hypothalamic area, dorsal hypothalamus, mammillary complex, dorsomedial anterior thalamus, ventral tegmental area, interpeduncular nucleus, raphe nucleus, torus semicircularis pars laminaris, reptilian A8 nucleus/ substantia nigra and central gray. For instance, only the medial septal nucleus projected substantially to the thalamus whereas the anterior septum was the only nucleus projecting to the caudal midbrain including the central gray. The anterior and lateral septal nuclei also differ in the way in which their projection to the preoptic hypothalamus terminated. The midline septal division is composed of the dorsal septal nucleus, nucleus septalis impar and nucleus of the posterior pallial commissure. The latter two nuclei projected to the lateral habenula and, at least the nucleus of the posterior pallial commissure, to the mammillary complex. The dorsal septal nucleus projected to the preoptic and periventricular hypothalamus and the anterior thalamus, but its central part seemed to project to the caudal midbrain (up to the midbrain central gray). Finally, the ventromedial septal division (ventromedial septal nucleus) showed a massive projection to the anterior and the lateral tuberomammillary hypothalamus.Data on the connections of the septum of P. hispanica and Gecko gekko are discussed from a comparative point of view and used for better understanding of the functional anatomy of the tetrapodian septum. J. Comp. Neurol. 401:525–548, 1998. © 1998 Wiley-Liss, Inc.
In order to examine whether the entorhinal-hippocampal-entorhinal circuit is reciprocal and topographic, the connections between the subiculum, the CA1 field, and the entorhinal cortex were studied with the carbocyanine dye (Dil), which moves in both retrograde and anterograde directions. We investigated the organization of reciprocal connections revealed by injections of Dil in the entorhinal cortex along the rhinal sulcus. Anterograde fluorescent labeling showed the same pattern reported in previous studies of the dorsal hippocampus. When the injection site of DiI extended into the deep layers (IV–VI) of the same cortical column, the anterograde labeling of the perforant path was accompanied by retrograde labeling of the subicular neurons and the CA1 neurons. The distribution of labeled cells overlapped the distribution of labeled fibers, and the distribution of labeled cells paralleled that of the labeled fibers in the CA1 field. DiI injection into the medial entorhinal cortex revealed fewer retrogradely labeled subicular neurons than injection into the lateral entorhinal cortex, whereas the number of labeled CA1 neurons was not dependent on the injection site. The number of labeled CA1 neurons was always several times greater than the number of subicular neurons. Thus, the amount of information conveyed by the CA1 projection might be higher than that conveyed by the subicular projection. These results indicate that the entorhinal cortex, CA1, and the subiculum are connected reciprocally and topographically. We believe that the framework of the major hippocampal circuit proposed in previous studies should be reconsidered. We propose that the CA1 projection, rather than the subicular projection, is the main projection that feeds back information from the hippocampus to the entorhinal cortex. © 1995 Wiley-Liss, Inc.
A detailed analysis of the cortical projections of the medial septum-diagonal band (MS/DB) complex was carried out by means of anterograde transport of Phaseolus vulgaris leucoagglutinin (PHA-L). The tracer was injected iontophoretically into cell groups of the medial septum (MS) and the vertical and horizontal limbs of the diagonal band of Broca (VDB and HDB), and sections were processed immunohistochemically for the intra-axonally transported PHA-L. The labeled efferents showed remarkable differences in regional distribution in the cortical mantle dependent on the position of the injection site in the MS/DB complex, revealing a topographic organization of the MS/DB-cortical projection. In brief, the lateral and intermediate aspects of the HDB, also referred to as the magnocellular preoptic area, predominantly project to the olfactory nuclei and the lateral entorhinal cortex. The medial part of the HDB and adjacent caudal (angular) part of the VDB are characterized by widespread, abundant projections to medial mesolimbic, occipital, and lateral entorhinal cortices, olfactory bulb, and dorsal aspects of the subicular and hippocampal areas. Projections from the rostromedial part of the VDB and from the MS are preponderantly aimed at the entire hippocampal and retrohippocampal regions and to a lesser degree at the medial mesolimbic cortex. Furthermore, the MS projections are subject to a clear mediolateral topographic arrangement, such that the lateral MS predominantly projects to the ventral/temporal aspects of the subicular complex and hippocampus and to the medial portion of the entorhinal cortex, whereas more medially located cells in the MS innervate more septal/dorsal parts of the hippocampal and subicular areas and more lateral parts of the entorhinal cortex. PHA-L filled axons have been observed to course through a number of pathways, i. e., the fimbria-fornix system, supracallosal stria, olfactory peduncle, and lateral piriform route (the latter two mainly by the HDB and caudal VDB). Generally, labeled projections were distributed throughout all cortical layers, although clear patterns of lamination were present in several target areas. The richly branching fibers were abundantly provided with both “boutons en passant” and terminal boutons. Both distribution and morphology of the labeled basal forebrain efferents in the prefrontal, cingulate, and occipital cortices closely resemble the distribution and morphology of the cholinergic innervation as revealed by immunohistochemical demonstration of choline acetyltransferase. In contrast, the labeled projections to the olfactory, hippocampal, subicular, and entorhinal areas showed a heterogeneous morphology. Here, the distribution of only the thin varicose projections resembled the distribution of cholinergic fibers.
The projections from the caudal part of the medial frontal cortex, encompassing the prelimbic area (PL) and the infralimbic area (IL) (Brodmann's areas 32 and 25, respectively), were studied in the cat with the anterograde autoradiographic tracing technique. The results indicate that the projection fields of IL, in contrast to those of PL, are restricted almost exclusively to limbic structures.
Whereas the major thalamic projections from PL reach the mediodorsal, anteromedial, and ventromedial nuclei, the medial part of the lateral posterior nucleus, and the parataenial and reticular nuclei, and weak projections from this area are directed to the nucleus reuniens and other midline nuclei, the nucleus reuniens is the major thalamic termination field of fibers arising from IL. Cortical areas that are reached by fibers originating in PL and, to a lesser degree, also in IL, include more rostral prefrontal areas (areas 8, 6, and 12), the agranular insular, and the rostral perirhinal cortices. In contrast, cortical areas that are more strongly related to IL include the cingulate, retrosplenial, caudal entorhinal, and perirhinal cortices and the subiculum of the hippocampal formation. Another prominent output of PL concerns projections to an extensive medial part of the caudate nucleus and the ventral striatum, whereas fibers from IL only distribute most ventrally in the striatum. In the amygdaloid complex, fibers from PL were found to reach the basolateral, basomedial, and central nuclei, and fibers from IL to distribute to the medial and central nuclei. PL furthermore projects to the claustrum and the endopiriform nucleus. Other structures in the basal forebrain, including the medial septum, the nuclei of the diagonal band, the preoptic area, and the lateral and dorsal hypothalamus are densely innervated by IL and only sparsely by PL. With respect to more caudal parts of the brainstem, projections from PL and IL appeared to be essentially similar. They reach the ventral tegmental area, the periaqueductal gray, the parabrachial nucleus, and in cases of PL injections were followed as far caudally as the pons.
Pallial and subpallial morphological subdivisions of the developing chicken telencephalon were examined by means of gene markers, compared with their expression pattern in the mouse. Nested expression domains of the genes Dlx-2 and Nkx-2.1, plus Pax-6-expressing migrated cells, are characteristic for the mouse subpallium. The genes Pax-6, Tbr-1, and Emx-1 are expressed in the pallium. The pallio-subpallial boundary lies at the interface between the Tbr-1 and Dlx-2 expression domains. Differences in the expression topography of Tbr-1 and Emx-1 suggest the existence of a novel “ventral pallium” subdivision, which is an Emx-1-negative pallial territory intercalated between the striatum and the lateral pallium. Its derivatives in the mouse belong to the claustroamygdaloid complex. Chicken genes homologous to these mouse genes are expressed in topologically comparable patterns during development. The avian subpallium, called “paleostriatum,” shows nested Dlx-2 and Nkx-2.1 domains and migrated Pax-6-positive neurons; the avian pallium expresses Pax-6, Tbr-1, and Emx-1 and also contains a distinct Emx-1-negative ventral pallium, formed by the massive domain confusingly called “neostriatum.” These expression patterns extend into the septum and the archistriatum, as they do into the mouse septum and amygdala, suggesting that the concepts of pallium and subpallium can be extended to these areas. The similarity of such molecular profiles in the mouse and chicken pallium and subpallium points to common sets of causal determinants. These may underlie similar histogenetic specification processes and field homologies, including some comparable connectivity patterns. J. Comp. Neurol. 424:409–438, 2000. © 2000 Wiley-Liss, Inc.
High resolution light microscopic autoradiography was used, together with regional surveys and combined aeridine orange staining, to define in rat hippocampus cellular and subcellular sites of concentration and retention of 3H dexamethasone and to compare the topographic pattern of labeling with that of 3H corticosterone. Nuclear uptake of 3H dexamethasone in the hippocampus is demonstrated for the first time in vivo. With 3H dexamethasone, strongest nuclear radioactive labeling was observed in certain glial cells throughout the hippocampus, followed by strong nuclear labeling in most neurons in area CA1 and in the adjacent dorsolateral subiculum and weak nuclear labeling in granule cells of the dentate gyrus. Neurons in areas CA2, CA3, CA4, and in the dorsomedial subiculum and indusium griseum showed little or no nuclear labeling after 3H dexamethasone. With 3H corticosterone, strongest nuclear labeling was observed in neurons in area CA2 and in the dorsomedial subiculum and indusium griseum, followed by area CA1, then CA3 and CA4; the dentate gyrus contained scattered strongly labeled cells among cells with intermediate nuclear labeling. At the subcellular level, evidence for both nuclear and cytoplasmic accumulation of label was found. The results indicate that dexamethasone and corticosterone have both nuclear and cytoplasmic binding sites and that particular patterns of target cell distribution exist, characteristic for each agent. This suggests a differential regulation of cellular functions for the two compounds. Corticosterone nuclear binding appears to be more extensive and encompasses regions with dexamethasone binding. Whether in certain of these common regions corticosterone binds to the same receptor as dexamethasone, which seems possible, or to different receptors, remains to be clarified.
Orexin (ORX)-A and -B are recently identified neuropeptides, which are specifically localized in neurons within and around the lateral hypothalamic area (LHA) and dorsomedial hypothalamic nucleus (DMH), the regions classically implicated in feeding behavior. Here, we report a further study of the distribution of ORX-containing neurons in the adult rat brain to provide a general overview of the ORX neuronal system. Immunohistochemical study using anti-ORX antiserum showed ORX-immunoreactive (ir) neurons specifically localized within the hypothalamus, including the perifornical nucleus, LHA, DMH, and posterior hypothalamic area. ORX-ir axons and their varicose terminals showed a widespread distribution throughout the adult rat brain. ORX-ir nerve terminals were observed throughout the hypothalamus, including the arcuate nucleus and paraventricular hypothalamic nucleus, regions implicated in the regulation of feeding behavior. We also observed strong staining of ORX-ir varicose terminals in areas outside the hypothalamus, including the cerebral cortex, medial groups of the thalamus, circumventricular organs (subfornical organ and area postrema), limbic system (hippocampus, amygdala, and indusium griseum), and brain stem (locus coeruleus and raphe nuclei). These results indicate that the ORX system provides a link between the hypothalamus and other brain regions, and that ORX-containing LHA and DMH neurons play important roles in integrating the complex physiology underlying feeding behavior.
The Madagascan lesser hedgehog tenrec was investigated to get insight into the areal evolution of the hippocampal formation in mammals with poorly differentiated brains. The hippocampal subdivisions were analyzed using cyto- and chemoarchitectural criteria; long associational and commissural connections were demonstrated with tracer techniques. The hedgehog tenrec shows a well differentiated dentate gyrus, CA3 and CA1. Their major intrinsic connections lie within the band of variations known from other species. The dentate hilar region shows calretinin-positive mossy cells with extensive projections to the molecular layer. The calbindin- and enkephalin-positive granule mossy fibers form a distinct endbulb and do not invade the CA1 as reported in the erinaceous hedgehog. Isolated granule cells with basal dendrites were also noted. A CA2 region is hard to identify architecturally; its presence is suggested due to its contralateral connections. Subicular and perisubicular regions are clearly present along the dorsal aspects of the hemisphere, but we failed to identify them unequivocally along the caudal and ventral tip of the hippocampus. A temporal portion of the subiculum, if present, differs in its chemoarchitecture from its dorsal counterpart. The perisubicular region, located medially adjacent to the dorsal subiculum may be equivalent to the rat's presubiculum; evidence for the presence of a parasubiculum was rather weak.
Thesis (Ph. D. in Medical Sciences)--University of Tsukuba, (A), no. 2391, 2000.3.24 Joint authors: Takeshi Sakurai ... [et al.] Offprint. Originally published: Brain Research, v. 827, pp. 243-260, 1999 Includes supplementary treatices Includes bibliographical references
Direct projections primarily ipsilateral to hippocampus from medial septal, diagonal band, supramammillary, submammillothalamic, locus coeruleus, and dorsal and medianus raphe nuclei were demonstrated. The locus coeruleus projects primarily through the cingulum and fornix superior to the dorsal posterior hippocampus, with its terminal fields in the stratum lacunosum moleculare of the subiculum and areas CA 1-CA 2 of the dorsal posterior hippocampus. LC projections to the granular layer of the dentate hilus were not found. Raphe nuclei project through the cingulum, fornix superior, and primarily the fimbria, to the dorsal and ventral posterior hippocampus, with their terminal fields in the stratum lacunosum moleculare of the dorsal posterior subicular region, stratum radiatum of CA 1-CA 3 in the dorsal hippocampus, and the stratum polymorph of the dentate gyrus, primarily in its superficial part. Raphe projections to the anterior hippocampal rudiment were found. However, no projection was found to the subiculum of the ventral posterior hippocampus, nor to stratum oriens. Hypothalamic nuclei project through the fornix superior and the fimbria, mainly to the dorsal posterior hippocampus with abundant terminal fibers in the depth of the dentate hilus. Smaller cells in these hypothalamic nuclei appear projecting to the ventral hippocampus. The number of neurons in the entorhinal area, the diagonal band, and the hypothalamic nuclei projecting to the hippocampus suggests these groups as the main sources of the extrinsic hippocampal afferents. In addition, they may also serve as relay stations for inputs from more caudal nuclei, and the topographic organization of their terminal fields as described herein may have important functional implications.
An autoradiographic study of neuronal and glial production was carried out in the indusium griseum of mice. Most neurons were produced between 13 and 15 days post-conception. One part of the glial population underwent its last or second-last divisions between 14 and 16 days post-conception, while the other continued to undergo a number of divisions into postnatal life. It is suggested the former were astrocytes and the latter oligodendrocytes.
The structure and connections of areas within the olfactory peduncle (anterior olfactory nucleus and tenia tecta) have been examined. The anterior olfactory nucleus has been divided into external, lateral, dorsal, medial, and ventro-posterior parts. In spite of the term nucleus which is applied to these areas, all of them contain pyramidal-type cells with apical and basal dendrites oriented normal to the surface, and are essentially cortical in organization. Experiments utilizing retrograde and anterograde axonal transport of horseradish peroxidase (HRP) have demonstrated that each of these parts of the anterior olfactory nucleus possesses a unique pattern of afferent and efferent connections with other olfactory areas. All subdivisions have projections to both the ipsilateral and contralateral sides, although the ipsilateral projection of the pars externa (to the olfactory bulb) is extremely light. Interestingly, crossed projections are in each case directed predominantly to areas adjacent to the homotopic areas.
The ascending connections to the striatum and the cortex of the Tegu lizard, Tupinambis Nigropunctatus, were studied by means of anterograde fiber degeneration and retrograde axonal transport. The striatum receives projections by way of the dorsal peduncle of the lateral forebrain bundle from four dorsal thalamic nuclei: nucleus rotundus, nucleus reuniens, the posterior part of the dorsal lateral geniculate nucleus and nucleus dorsomedialis. The former three nuclei project to circumscribed areas of the dorsal striatum, whereas nucleus dorsomedialis has a distribution to the whole dorsal striatum. Other sources of origin to the striatum are the mesencephalic reticular formation, substantia nigra and nucleus cerebelli lateralis. With the exception of the latter afferentation all these projections are ipsilateral.
The ascending connections to the pallium originate for the major part from nucleus dorsolateralis anterior of the dorsal thalamus. The fibers course in both the medial forebrain bundle and the dorsal peduncle of the lateral forebrain bundle and terminate ipsilaterally in the middle of the molecular layer of the small-celled part of the mediodorsal cortex and bilaterally above the intermediate region of the dorsal cortex. The latter area is reached also by fibers from the septal area. The large-celled part of the mediodorsal cortex receives projections from nucleus raphes superior and the corpus mammillare.
A sensitive immunofluorescence technique was used to describe systematically the distrubution of dopamine-beta-hydroxylase (DBH)-containing cell bodies, non-terminal fiber pathways, and terminal fields in the brain of the male albino rat. DBH is the enzyme that catalyzes the conversion of dopamine to noradrenaline, and as such is useful as an anatomical marker for noradrenaline and possibly adrenaline neurons. The enzyme is not present in dopamine- or indolamine-containing neurons. Ten micron frozen sections (1-in 20 series) were prepared in the frontal, sagittal, and horizontal planes from the olfactory bulb to the upper cervical segments of the spinal cord; adjacent sections in each plane were stained for DBH and for cells (toluidine blue=azure II). An atlas consisting of 40 projection drawings of selected frontal sections illustrates the results of the investigation. DBH perikarya are confined to three groups in the pons and medulla: the well defined locus coeruleus, a more diffuse but continuous subcoeruleus group that arches through the pons and ventral medulla, and a third dorsal medullary group centered in the dorsal motor nucleus of the vagus. A single principal adrenergic fiber system distributes a great many of the axons from these neuron groups to a majority of nuclear areas in the brain. In the pons and medulla two components of the fiber system may be distinguished. A medullary branch may be followed from the posterior aspect of the subcoeruleus group dorsally and then anteriorly through the lateral tegmental field and ventral aspect of the vestibular complex to a position subjacent to the locus coeruleus, where it is joined by a subcoeruleus branch consisting of a large number of fibers coursing among cells along the length of the subcoeruleus group, and by fibers arising from the locus coeruleus. Anterior to the locus coeruleus the principal adrenergic bundle courses as a single fiber tract immediately ventrolateral to the central gray in the mesencephalon and in the zona incerta and substantia innominata in the diencephalon. At the level of the septal area separate bundles reach the cortex dorsally over the genu of the corpus calosum via the medial septal-diagonal band nuclei and the lateral septum and ventrally between the olfactory tubercle and caudate-putamen. In the medulla and pons adrenergic fibers undoubtedly course in both directions. Anterior to the most rostral pontine cell bodies, however, all fibers presumably ascend. Along the course of the bundle distinct branches emerge to innervate circumscribed terminal fields. In addition, certain regions of the brain such as the reticular formation and pontine gray receive diffuse DBH innervation derived from less clearly defined pathways. A small number of areas in the brain contain little or no detectable DBH. These include the caudate-putamen, nucleus accumbens, globus pallidus, olfactory tubercle, subthalamic nucleus, substantia nigra, pretectal area, third, fourth and sixth cranial verve nuclei, and the trapezoid body nucleus.
The immunocytochemical features of the indusium griseum (IG) were compared with the corresponding hippocampus in 5 patients with Alzheimer's disease (AD) and 5 age-matched nondemented individuals using antibodies against beta-amyloid, the A68 protein (Alz-50 antibody), tau, ubiquitin and synapsin I. beta-Amyloid-positive plaques were prominent in the AD hippocampus but were not present in the IG. Numerous Alz-50, tau and ubiquitin-positive neurofibrillary tangles and dystrophic neurites were observed in the AD hippocampus but were infrequent in the IG. Synapsin I immunoreactivity was significantly reduced in both the AD hippocampus and the AD IG when compared to age-matched patients. These findings suggest that the IG may be resistant to factors that trigger production of abnormal AD-associated proteins. Loss of synaptic input alone may not account for the AD-associated changes in the hippocampus since synaptic depletion was seen in both the hippocampus and the unaffected AD IG.
Using retrograde axonal flow and wheatgerm agglutinin conjugated to horseradish peroxidase, we studied the distribution of cortical neurons giving rise to spinal and dorsal column nuclear projections, and correlated the regions involved in the projections with the cytoarchitectonic areas recently identified in the lesser hedgehog tenrec, Echinops telfairi (Insectivora). Labeled cortical neurons were most numerous following injections of tracer into higher cervical segments, whereas almost none were found following thoracic injections. The cortical labeling appeared more prominent ipsilaterally than contralaterally after spinal injections, although it was more prominent on the contralateral side after injection into the dorsal column nuclear complex. The majority of labeled neurons found in lamina V occupied the neocortex adjacent to the interhemispheric fissure along the rostrocaudal extent of the small corpus callosum. This location corresponded to an intermediate rostrocaudal portion of the hemisphere, and particularly to area 2 of Rehkämper. In some cases, adjacent portions of areas 1 and 3 were also involved, as well as neocortical regions of the lateral hemisphere. The present data did not suggest a somatotopic organization of the projections; likewise, evidence for the presence of more than one somatosensorimotor representation was sparse.
The projections of the supramammillary nucleus (SUM) were examined in the rat by the anterograde anatomical tracer Phaseolus vulgaris leucoagglutinin (PHA-L). The majority of labeled fibers from SUM ascended through the forebrain within the medial forebrain bundle. SUM fibers were found to terminate heavily in the hippocampal formation, specifically within the granule cell layer and immediately adjoining molecular layer of the dentate gyrus. In addition, SUM fibers were shown to distribute densely to several structures with strong connections with the hippocampus, namely, the nucleus reuniens of the thalamus, the medial and lateral septum, the entorhinal cortex, and the endopiriform nucleus.
SUM fibers were also shown to project significantly to several additional subcortical and cortical sites. The subcortical sites were the dorsal raphe nucleus, the midbrain central gray, the fields of Forel/zona incerta, the dorsomedial hypothalamic area, midline/intralaminar nuclei of the thalamus (posterior paraventricular, rhomboid, central medial, intermediodorsal, and mediodorsal), the medial and lateral preoptic areas, the bed nucleus of the stria terminalis, the substantia innominata, the vertical limb of the diagonal band nucleus, and the claustrum. The cortical sites were the occipital, temporal, parietal, and frontal cortices.
Some notable differences were observed in projections from the lateral as compared to the medial SUM. For example, fibers originating from the lateral SUM distributed heavily to the hippocampal formation and parts of the cortex, whereas those from the medial SUM projected sparsely to these two regions.
The SUM projections to the hippocampal formation and associated structures may serve as the substrate for a SUM involvement in the generation of the theta rhythm of the hippocampus and the gating of information flow through the hippocampal formation.
The hippocampus has previously been shown to influence cardiovascular function, and this effect appears to be mediated by the connection the hippocampus has with the infralimbic area of the medial frontal cortex (MFC), a region which projects directly to the nucleus of the solitary tract (NTS) in the dorsal medulla. In the present study, anatomical and electrophysiological techniques were utilized to determine the degree of convergence of hippocampal input to the MFC on neurons in the MFC which project to the NTS. Injections of the anterograde and retrograde neuroanatomical tracer wheat-germ agglutinin-horseradish peroxidase (WGA-HRP) into the NTS retrogradely labelled cells in the infralimbic and prelimbic regions of the MFC. Injections of WGA-HRP into the ventral hippocampus anterogradely labelled terminals in the MFC which, at the light microscopic level, closely overlapped the origin of the descending projection from the MFC to the brainstem. Electron microscopic analysis revealed that anterogradely labelled terminals make synaptic contact primarily on dendritic processes in the neuropil adjacent to retrogradely labelled cells. In addition, anterogradely labelled terminals did, in some cases, make synaptic contact on the somas of retrogradely labelled cells. Electrical stimulation of the NTS antidromically activated cells in the infralimbic and prelimbic areas of the MFC. The average latency of antidromic activation was 30 msec, corresponding to a conduction velocity of approximately 0.7 m/s. Electrical stimulation of the ventral hippocampus orthodromically activated cells in the MFC. With an appropriate delay between the hippocampal and NTS stimuli, the orthodromic and antidromic potentials could be made to collide. The results of this study establish a structural as well as functional link between the hippocampus and NTS-projection neurons in the MFC.
The efferent projections of the infralimbic region (IL) of the medial prefrontal cortex of the rat were examined by using the anterograde transport of Phaseolus vulgaris leucoagglutinin (PHA-L). Major targets of the IL were found to include the agranular insular cortex, olfactory tubercle, perirhinal cortex, the whole amygdaloid complex, caudate putamen, accumbens nucleus, bed nucleus of the stria terminalis, midline thalamic nuclei, the lateral preoptic nucleus, paraventricular nucleus, supramammillary nucleus, medial mammillary nucleus, dorsal and posterior areas of the hypothalamus, ventral tegmental area, central gray, interpeduncular nucleus, dorsal raphe, lateral parabrachial nucleus and locus coeruleus. Previously unreported projections of the IL to the anterior olfactory nucleus, piriform cortex, anterior hypothalamic area and lateroanterior hypothalamic nucleus were observed. The density of labeled terminals was especially high in the agranular insular cortex, olfactory tubercle, medial division of the mediodorsal nucleus of the thalamus, dorsal hypothalamic area and the lateral division of the central amygdaloid nucleus. Several physiological and pharmacological studies have suggested that the IL functions as the 'visceral motor' cortex, involved in autonomic integration with behavioral and emotional events. The present investigation is the first comprehensive study of the IL efferent projections to support this concept.
Projections of the hippocampal formation to the prefrontal cortex were visualized in the rat by means of the anterograde tracer Phaseolus vulgaris-leucoagglutinin. These projections distribute only to the prelimbic and the medial orbital cortices and arise exclusively from restricted portions of field CA1 of the Ammon's horn and the subiculum. The most dorsal portion of CA1 does not contribute fibers to this projection. In the subiculum, its origin is restricted to the proximal half, i.e., the portion that directly borders field CA1. Fibers from field CA1 and the subiculum have comparable distribution patterns in the prelimbic and medial orbital cortices. The density and distribution in the prefrontal cortex of the projections from the proximal portion of the subiculum depends on the location of the injections along the dorsoventral axis of the hippocampal formation: the intermediate portion of the subiculum projects more densely and diffusely than its dorsal and ventral portions.
In the prelimbic cortex, labeled fibers are present in all layers, showing marked morphological differences in deep versus superficial layers. In layers V and VI, most of the fibers are vertically oriented, while in layers II and III they are short and oriented towards the pial surface. Although no clear differences in terminal distribution were observed along the rostrocaudal extent of the prelimbic cortex, its dorsal and ventral portions show different innervation patterns. In the ventral portion of the prelimbic cortex, varicose fibers and terminal arborizations were present in all cortical layers, deep (V and VI) as well as superficial (II and III). In its dorsal part, the innervation was less dense and mostly present in the deep layers (V and VI). The fiber and terminal distribution in the medial orbital cortex was diffuse in all layers with a slight preference for layers deep to layer II.
This paper describes the distribution of structures stained with mono- and polyclonal antibodies to the calcium-binding proteins calbindin D-28k and parvalbumin in the nervous system of adult rats. As a general characterization it can be stated that calbindin antibodies mainly label cells with thin, unmyelinated axons projecting in a diffuse manner. On the other hand, parvalbumin mostly occurs in cells with thick, myelinated axons and restricted, focused projection fields. The distinctive staining with antibodies against these two proteins can be observed throughout the nervous system.
Medial agranular cortex (AGm) is a narrow, longitudinally oriented region known to have extensive corticocortical connections. The rostral and caudal portions of AGm exhibit functional differences that may involve these connections. Therefore we have examined the rostrocaudal organization of the afferent cortical connections of AGm by using fluorescent tracers, to determine whether there are significant differences between rostral and caudal AGm. Mediolateral patterns have also been examined in order to compare the pattern of corticocortical connections of AGm to those of the laterally adjacent lateral agranular cortex (AGl) and medially adjacent anterior cingulate area (AC).
In order to study the morphological substrate of possible thalamic influence on the cells of origin and area of termination of the projection from the entorhinal cortex to the hippocampal formation, we examined the pathways, terminal distribution, and ultrastructure of the innervation of the hippocampal formation and parahippocampal region by the nucleus reuniens of the thalamus (NRT). We employed anterograde tracing with Phaseolus vulgaris-leucoagglutinin (PHA-L). Injections of PHA-L in the NRT produce fiber and terminal labeling in the stratum lacunosum-moleculare of field CA1 of the hippocampus, the molecular layer of the subiculum, layers I and III/IV of the dorsal subdivision of the lateral entorhinal area (DLEA), and layers I and III-VI of the ventral lateral (VLEA) and medial (MEA) divisions of the entorhinal cortex. Terminal labeling is most dense in the stratum lacunosum-moleculare of field CA1, the molecular layer of the ventral part of the subiculum, MEA, and layer I of the perirhinal cortex. In layer I of the caudal part of DLEA and in MEA, terminal labeling is present in clusters. Injections in the rostral half of the NRT produce the same distribution in the hippocampal region as those in the caudal half of the NRT, although the projections from the rostral half of the NRT are much stronger. A topographical organization is present in the projections from the head of the NRT, so that the dorsal part projects predominantly to dorsal parts of field CA1 and the subiculum and to lateral parts of the entorhinal cortex, whereas the ventral part projects in greatest volume to ventral parts of field CA1 and the subiculum and to medial parts of the entorhinal cortex.
The connections of the lateral cortex of the lizard Podarcis hispanica have been traced using horseradish peroxidase transport techniques. After injections, restricted to the lateral cortex, labelled neurons can be observed bilaterally in the main olfactory bulbs and the diagonal band, contralaterally in the lateral cortex and ipsilaterally in the nucleus of the lateral olfactory tract, the ventral amygdaloid nucleus and also in the area triangularis. An efferent has also been shown on the ipsilateral medial cortex. This pattern of connections supports the hypothesis that the reptilian lateral cortex is comparable to the entorhinal and piriform cortex of mammals.
The projections from the rat medial prefrontal cortex to the amygdaloid complex were investigated using retrograde transport of fluorescent dyes and anterograde transport of horseradish peroxidase-WGA. The ventral anterior cingulate, prelimbic, infralimbic and medial orbital areas and the taenia tecta were found to project to the amygdaloid complex. The projections from the prelimbic area arose bilaterally. The medial orbital, prelimbic and anterior cingulate areas send convergent projections to the basolateral nucleus. The prelimbic area has additional projections to the posterolateral cortical nucleus and amygdalo-hippocampal area. The infralimbic area does not project to the basolateral nucleus and cortico-amygdaloid projections from this area are focussed on the anterior cortical nucleus and the anterior amygdaloid area. Both prelimbic and infralimbic areas project to an area situated between the central, medial and basomedial nuclei. Based on similar projections, this area appears to be a caudal continuation of the anterior amygdaloid area. The results indicate that the medial prefrontal component of the "basolateral limbic circuit" is restricted to the anterior cingulate and prelimbic areas. No evidence was obtained to support the existence of a medial prefronto-amygdaloid component of the "visceral forebrain".
The organization of subcortical inputs to the parahippocampal cortex, which in the present study in the cat is considered to comprise the entorhinal and perirhinal cortices, was studied by using retrograde and anterograde tracing techniques. The results of the retrograde tracer horseradish peroxidase (HRP), HRP conjugated with wheat germ agglutinine (WGA-HRP), Fast Blue (FB) or Nuclear Yellow (NY] injections indicate that the entorhinal and perirhinal cortices receive inputs from the magnocellular basal forebrain and from distinct portions of the amygdaloid complex, the claustrum, and the thalamus. The two cortices are further projected upon by fibers from the supramamillary region of the hypothalamus, the ventral tegmental area of the mesencephalon, the dorsal raphe nucleus, the nucleus centralis superior, and the locus coeruleus. The entorhinal cortex, in addition, receives projections from the medial septum. As regards the projections from the amygdaloid complex, it was observed that the entorhinal cortex receives its heaviest input from the basolateral amygdaloid nucleus, whereas the perirhinal cortex receives a strong projection from the lateral nucleus and a weaker projection from the basomedial nucleus of the amygdala. Of the thalamic nuclei that project to the parahippocampal cortex, the nucleus reuniens is only connected with the entorhinal cortex, while fibers from the medial geniculate nucleus and the lateral posterior nucleus terminate in the perirhinal cortex. Injections of tritiated amino acid (3H-leucine) were placed in the medial septum, the dorsal and ventral claustrum, the basolateral and basomedial amygdaloid nuclei, and the nucleus reuniens of the thalamus. The results of these experiments demonstrate that, with the exception of the claustrum, these subcortical areas project mainly to the superficial layers I-III and the lamina dissecans of the parahippocampal cortex, and to a lesser degree to the deep layers V and VI.
In the present study in the cat the parahippocampal cortex denotes the caudoventral part of the limbic lobe and is composed of the entorhinal and perirhinal cortices. The cytoarchitecture of these areas and their borders with adjacent cortical areas are briefly discussed. The organization of the cortical afferents of the parahippocampal cortex was studied with the aid of retrograde and anterograde tracing techniques. In order to identify the source of cortical afferents, injections of retrograde tracers such as wheat germ agglutinin conjugated with horseradish peroxidase (WGA-HRP), or the fluorescent substances fast blue or nuclear yellow, were placed in different parts of the parahippocampal cortex. In an attempt to further disclose the topographical and laminar organization of the afferent pathways, injections of tritiated amino acids were placed in cortical areas that were found to project to the parahippocampal cortex. The results of these experiments indicate that fibers from olfactory-related areas, the hippocampus, and other parts of the limbic cortex project only to the entorhinal cortex. The afferents from olfactory structures terminate predominantly superficially, whereas hippocampal and limbic cortical afferents are directed mainly to layers deep to the lamina dissecans. Paralimbic areas, including the anterior cingulate and the prelimbic cortices on the medial aspect, and the orbitofrontal and granular and agranular insular cortices on the lateral aspect of the hemisphere, project to the entorhinal cortex and medial parts of area 35 of the perirhinal cortex. These mostly mesocortical afferents terminate in both the superficial and deep layers of the entorhinal and perirhinal cortices. Parasensory association areas, which form part of the neocortex, do not project farther medially in the parahippocampal cortex than the perirhinal areas 35 and 36. These afferents mainly stem from a rather wide rim of neocortex that lies directly adjacent to area 36 and extends from the posterior sylvian gyrus via the posterior ectosylvian gyrus into the posterior suprasylvian gyrus. There is a rostrocaudal topographical arrangement in these projections such that rostral cortical areas distribute more rostrally and caudal parts project to more caudal parts of the perirhinal cortex. The cortex of the posterior suprasylvian gyrus contains the paravisual areas 20 and 21. The posterior sylvian gyrus most probably represents a para-auditory association area, whereas the most ventral part of the posterior ectosylvian gyrus may constitute a convergence area for visual and auditory inputs.(ABSTRACT TRUNCATED AT 400 WORDS)
The thalamic projections to the hippocampal formation and to the subicular and entorhinal areas in the cat have been studied with retrograde transport of horseradish peroxidase (HRP) or wheat germ agglutinin conjugated to HRP (WGA-HRP) and anterograde transport of WGA-HRP. Retrograde transport tracers injected in various parts of these cortices resulted in labeled cells in the midline, anterior, and lateral dorsal nuclei. Injections into the hippocampal formation or the subiculum led to retrograde labeling of cells in the reuniens nucleus of the ipsilateral thalamus throughout its rostrocaudal extent, whereas the restricted injections into the dentate gyrus and the inferior region of the hippocampus led to no labeling. Following an injection into the pre- and parasubiculum, a large number of labeled cells were seen not only in the reuniens nucleus but in other midline nuclei. In addition, a substantial number of labeled cells were also detected in the anterior and lateral dorsal nuclei, particularly in the anterodorsal nucleus, which contained densely arranged labeled cells throughout almost the entire rostrocaudal extent. An injection into the medial entorhinal area labeled a number of cells in the anterior nuclei and in the reuniens nucleus, particularly its dorsal part. Injections into various subdivisions of the lateral entorhinal area yielded different patterns of distribution of labeled cells in the thalamic nuclei. An injection into the ventromedial division (VMEA) led to abundant labeling of cells in the paraventricular and reuniens nuclei. After an injection into the ventral division (VLEA), numerous labeled cells were detected in the reuniens nucleus and a lesser number in the paraventricular nucleus at anterior levels. When an injection was made into the dorsal division (DLEA), a large number of labeled cells were detected in the reuniens nucleus, and less numerous labeled cells were found in the central medial nucleus. There appears to be a topographic arrangement of cortical projections of the reuniens nucleus. The pre- and parasubiculum receive projections from the most medial part of the reuniens nucleus near the midline, and the DLEA receives projections from the medial part of the nucleus. The cells projecting to the VLEA and MEA are distributed in the central part of the reuniens nucleus, and those to the VMEA are distributed in the lateral part. Anterograde experiments were also performed; injections of WGA-HRP into the reuniens nucleus resulted in terminal labeling in the superficial layers of the subicular area and the neighboring hippocampus and in the entorhinal area.
The cells of origin and projection fields of the descending afferents to the mammillary nuclei were studied in the rat with retrograde and anterograde transport of wheat germ agglutinin conjugated to horseradish peroxidase.
The subiculum projects bilaterally to the entire medial mammillary nucleus (MM) in a topographic fashion along the two axes: (1) the proximal part of the subiculum along the presubiculo-CA1 axis projects to the caudal and lateral regions of the MM whereas the more distal part of the subiculum projects to the medial region; (2) the septal part of the subiculum projects to the caudodorsal region of the MM whereas the more temporal part projects progressively to the more rostroventral regions. The ventral subiculum also projects ipsilaterally to the ventral and lateral margin of the lateral mammillary nucleus (LM). The presubiculum projects bilaterally to the dorsolateral region of the pars posterior of the MM and ipsilaterally to the LM. The infralimbic cortex projects bilaterally to the rostrodorsal region of the MM, whereas the retrosplenial cortex (areas 29a and 29b) projects bilaterally to the medial region at the midrostrocaudal and middorsoventral levels of the MM. The nucleus of the diagonal band projects bilaterally to the caudomedial region of the MM, whereas the lateral septal nucleus projects bilaterally to the pars mediana and the mammillary fiber capsule. A part of the anterior hypothalamic area ventromedial to the fornix projects predominantly ipsilaterally to the rostroventral part of the MM, whereas other basal forebrain regions such as the bed nucleus of the stria terminalis, the medial preoptic and anterior hypothalamic areas, and the area of the tuber cinereum send fibers predominantly ipsilaterally to the mammillary fiber capsule.
The results reveal a complex organization of the descending projections to the mammillary nuclei, which may reflect the complex functions of these nuclei within the limbic circuitry.