Walter B Hoover

Florida Atlantic University, Boca Raton, FL, United States

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Publications (12)48.34 Total impact

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    ABSTRACT: As is well recognized, serotonergic (5-HT) fibers distribute widely throughout the brain, including the cerebral cortex. Although some early reports described the 5-HT innervation of the prefrontal cortex (PFC) in rats, the focus was on sensorimotor regions and not on the 'limbic' PFC - or on the medial, orbital and insular cortices. In addition, no reports have described the distribution of 5-HT fibers to PFC in rats using antisera to the serotonin transporter (SERT). Using immunostaining for SERT, we examined the pattern of distribution of 5-HT fibers to the medial, orbital and insular cortices in the rat. We show that 5-HT fibers distribute massively throughout all divisions of the PFC, with distinct laminar variations. Specifically, 5-HT fibers were densely concentrated in superficial (layer 1) and deep (layers 5/6) of the PFC but less heavily so in intermediate layers (layers 2/3). This pattern was most pronounced in the orbital cortex, particularly in the ventral and ventrolateral orbital cortices. With the emergence of granular divisions of the insular cortex, the granular cell layer (layer 4) was readily identifiable by a dense band of labeling confined to it, separating layer 4 from less heavily labeled superficial and deep layers. The pattern of 5-HT innervation of medial, orbital and insular cortices significantly differed from that of sensorimotor regions of the PFC. Serotonergic labeling was much denser overall in limbic compared to non-limbic regions of the PFC, as was striking demonstrated by the generally weaker labeling in layers 1-3 of the primary sensory and motor cortices. The massive serotonergic innervation of the medial, orbital and insular divisions of the PFC likely contributes substantially to well established serotonergic effects on affective and cognitive functions, including a key role in many neurological and psychiatric diseases.
    Journal of chemical neuroanatomy 01/2013; · 1.75 Impact Factor
  • R P Vertes, W B Hoover, J J Rodriguez
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    ABSTRACT: The central medial nucleus (CM) of thalamus is a prominent cell group of the rostral intralaminar complex of the thalamus. No previous report in the rat has comprehensively described the projections of CM. Using the anterograde anatomical tracer, Phaseolus vulgaris leucoagglutinin, we examined the efferent projections of CM, comparing projections from rostral (CMr) and caudal (CMc) regions of CM. We showed that the central medial nucleus distributes substantially to several cortical sites and to a limited number of subcortical structures. The primary CM targets were anterior and posterior regions of cortex, the claustrum, the caudate-putamen, the nucleus accumbens (ACC), the olfactory tubercle, and the amygdala. CMr and CMc distribute to several of the same structures but essentially to different parts of these structures. By comparison, CMr more strongly targets limbic structures, CMc more heavily sensorimotor structures. Main CMr projection sites were the medial agranular, anterior cingulate, prelimbic, dorsolateral orbital and dorsal agranular insular cortices, the dorsal striatum, the ACC, and the basolateral nucleus of the amygdala. Main CMc cortical projection sites were the ventrolateral, lateral and dorsolateral orbital cortices, dorsal, ventral and posterior agranular insular cortices, visceral cortex, primary somatosensory and motor cortices, and perirhinal cortex. Main CMc subcortical projection sites were the dorsal striatum and the lateral, central, anterior cortical, and basomedial nuclei of amygdala. The largely complementary output of CMr and CMc to diverse areas of cortex and to regions of the striatum and amygdala suggest a combined CM influence over a widespread area of the anterior cortex and throughout the dorsal and ventral striatum and the amygdala. CM projections to limbic and sensorimotor structures of the rostral forebrain suggest that CM may serve to integrate affective, cognitive and sensorimotor functions for goal-directed behavior.
    Neuroscience 05/2012; 219:120-36. · 3.12 Impact Factor
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    ABSTRACT: NMDAR antagonists can evoke delta frequency bursting in the nucleus reticularis of the thalamus (nRT). The mechanism of this oscillation was determined; antagonist blocks an NR2C-like conductance that has low Mg block at resting potential and thus can contribute a resting inward current in response to ambient glutamate. Block of this current hyperpolarizes the cell, deinactivating T-type Ca channels and thus triggering delta frequency bursting. The basis for assuming a NR2C-like conductance was that (1) transcripts for NR2C are abundant in the thalamus and (2) the current-voltage curve of the synaptically evoked NMDAR current has the low rectification characteristic of NR2C. In the current study, we have sought to determine whether the channels that generate the NMDAR current are NR2C-like or are actually comprised of receptors containing NR2C. We studied the current-voltage curve of synaptically evoked NMDAR current in the nRT of NR2C knockout mice. In wild-type mice, the current was weakly voltage dependent, as previously observed in rats. This weak rectification was absent in NR2C KO mice. In contrast, NR2C KO had no effect on the strongly rectifying NMDAR current in pyramidal cells of the prefrontal cortex. These results demonstrate that the low rectification normally observed in the nRT is due to NR2C.
    PLoS ONE 01/2012; 7(7):e41908. · 3.73 Impact Factor
  • Walter B Hoover, Robert P Vertes
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    ABSTRACT: The nucleus reuniens (RE) of the midline thalamus has been shown to strongly innervate structures of the limbic forebrain, prominently including the hippocampus (HF) and the medial prefrontal cortex (mPFC) and to exert pronounced excitatory effects on HF and mPFC. It was unknown, however, whether RE projections to, and hence actions on, the HF and mPFC originate from a common or largely separate groups of RE neurons. Using fluorescent retrograde tracing techniques, we examined the patterns of distribution of RE cells projecting to HF, to the mPFC or to both sites via axon collaterals. Specifically, injections of the retrograde tracers Fluorogold (FG) or Fluororuby (FR) were made in the mPFC and in various subfields of HF and patterns of single (FG or FR) or double labeled (FG + FR) cells in RE were determined. Pronounced numbers of (single) labeled neurons were present throughout RE with FG or FR injections, and although intermingled in RE, cells projecting to the mPFC were preferentially distributed along the midline or in the perireuniens nucleus (pRE), whereas those projecting to HF occupied a wide mediolateral cross sectional area of RE lying between cells projecting to the mPFC. Approximately, tenfold more labeled cells were present in RE with ventral compared to dorsal CA1 injections. Like single labeled neurons, double labeled cells were found throughout RE, but were most densely concentrated in areas of greatest overlap of FG+ and FR+ neurons or mainly in the lateral one-third of RE, medial to pRE. Depending on specific combinations of injections, double labeled cells ranged from approximately 3-9% of the labeled neurons. The nucleus reuniens has been shown to be a vital link in limbic subcortical-cortical communication and recent evidence indicates a direct RE involvement in hippocampal and medial prefrontal cortical-dependent behaviors. The present findings indicate that RE is critically positioned to influence the HF and mPFC, and their associated behaviors, via separate or collateral projections to these sites.
    Brain Structure and Function 09/2011; 217(2):191-209. · 7.84 Impact Factor
  • Walter B Hoover, Robert P Vertes
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    ABSTRACT: The medial orbital (MO) and ventral orbital (VO) cortices are prominent divisions of the orbitomedial prefrontal cortex. To our knowledge, no previous report in the rat has comprehensively described the projections of MO and VO. By using the anterograde tracer Phaseolus vulgaris leucoagglutinin and the retrograde tracer Fluoro-Gold, we examined the efferent projections of MO and VO in the rat. Although MO and VO projections overlap, MO distributes more widely throughout the brain, particularly to limbic structures, than does VO. The main cortical targets of MO were the orbital, ventral medial prefrontal (mPFC), agranular insular, piriform, retrosplenial, and parahippocampal cortices. The main subcortical targets of MO were the medial striatum, olfactory tubercle, claustrum, nucleus accumbens, septum, substantia innominata, lateral preoptic area, and diagonal band nuclei of the basal forebrain; central, medial, cortical, and basal nuclei of amygdala; paratenial, mediodorsal, and reuniens nuclei of the thalamus; posterior, supramammillary, and lateral nuclei of the hypothalamus; and periaqueductal gray, ventral tegmental area, substantia nigra, dorsal and median raphe, laterodorsal tegmental, and incertus nuclei of the brainstem. By comparison, VO distributes to some of these same sites, notably to the striatum, but lacks projections to parts of limbic cortex, to nucleus accumbens, and to the amygdala. VO distributes much more strongly, however, than MO to the medial (frontal) agranular, anterior cingulate, sensorimotor, posterior parietal, lateral agranular retrosplenial, and temporal association cortices. The patterns of MO projections are similar to those of the mPFC, whereas the projections of VO overlap with those of the ventrolateral orbital cortex (VLO). This suggests that MO serves functions comparable to those of the mPFC, such as goal-directed behavior, and VO performs functions similar to VLO such as directed attention. MO/VO may also serve as a link between lateral orbital and medial prefrontal cortices.
    The Journal of Comparative Neurology 07/2011; 519(18):3766-801. · 3.66 Impact Factor
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    ABSTRACT: The reticular nucleus (RT) of the thalamus, a thin sheet of GABAergic neurons located between the external medullary lamina and the internal capsule of the thalamus, has functionally distinct afferent and efferent connections with thalamic nuclei, the neocortex, the basal forebrain and the brainstem. RT is critically positioned to rhythmically pace thalamocortical networks leading to the generation of spindle activity during the early phases of sleep and during absence (spike-wave) seizures. Serotonin, acting on 5-HT(1A) receptors on parvalbumin-containing cells of RT, has been implicated in this rhythmicity. However, the precise source(s) of 5-HT afferents to the RT remains to be determined. In the present study, we injected the retrograde tracer, Fluorogold, into dorsal and ventral regions of RT to determine the origins of raphe input to RT. We further characterized the distribution of 5-HT fibers to RT by using immunohistochemistry for 5-HT and for the 5HT transporter (SERT) detection. Finally, we described the presence of the two major postsynaptic 5-HT receptors in RT, 5-HT(1A) and 5-HT(2A) receptors. Our results show that the dorsal raphe nucleus and the supralemniscal nucleus (B9) of the midbrain are the principal sources of raphe projections to RT. In addition, serotonergic fibers (5-HT and SERT positive) were richly distributed throughout RT, and 5-HT(1A) and 5-HT(2A) receptors were highly expressed on RT neurons and dendrites. These findings suggest a significant 5-HT modulatory influence on GABAergic neurons of RT in the control of rhythmical (or spindle) activity in thalamocortical systems directly associated with sleep and possibly with absence seizures.
    Synapse 02/2011; 65(9):919-28. · 2.31 Impact Factor
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    ABSTRACT: It is well established that serotonergic (5-hydroxytryptamine, 5-HT) fibers, mainly originating from the dorsal and median raphe nuclei of the brainstem, distribute throughout the forebrain, most heavily to 'limbic' forebrain structures. Few reports have examined the distribution of 5-HT fibers to the thalamus and none to our knowledge using immunoprocedures for the detection of the serotonin transporter (SERT)-a very sensitive marker for 5-HT fibers. Using immunohistochemical methods for SERT, we examined the pattern of distribution of 5-HT fibers to the thalamus in the rat. We show that serotonergic fibers are heavily concentrated in midline, intralaminar and association nuclei of the thalamus, and with the exception of the lateral geniculate complex, weakly distributed to principal nuclei of thalamus. Specifically, we demonstrate that 5-HT fibers are densely concentrated in the anteroventral, anteromedial and interanteromedial nuclei of the anterior thalamus, the paraventricular, rhomboid and reuniens nuclei of the midline thalamus, the central medial and central lateral nuclei of the intralaminar thalamus, the intermediodorsal nucleus, the lateral dorsal nucleus, and the dorsal and ventral lateral geniculate nuclei and intergeniculate leaflet of the LGN complex. Less densely innervated sites include the mediodorsal, paracentral, parafascicular, lateral posterior and submedial nuclei of thalamus. Remaining regions of the thalamus, largely consisting of principal nuclei, contained few 5-HT fibers. This pattern of 5-HT innervation indicates that serotonin/ serotonergic fibers mainly affect thalamic nuclei with connections to 'non-principal' or limbic regions of the cortex (or forebrain). This suggests that serotonergic fibers to the thalamus may exert a significant influence on affective and cognitive functions, possibly complementing the actions of 5-HT fibers to other parts of the brain involved in emotional and cognitive behaviors.
    Brain Structure and Function 04/2010; 215(1):1-28. · 7.84 Impact Factor
  • Robert P Vertes, Walter B Hoover
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    ABSTRACT: The paraventricular (PV) and paratenial (PT) nuclei are prominent cell groups of the midline thalamus. To our knowledge, only a single early report has examined PV projections and no previous study has comprehensively analyzed PT projections. By using the anterograde anatomical tracer, Phaseolus vulgaris leucoagglutinin, and the retrograde tracer, FluoroGold, we examined the efferent projections of PV and PT. We showed that the output of PV is virtually directed to a discrete set of limbic forebrain structures, including 'limbic' regions of the cortex. These include the infralimbic, prelimbic, dorsal agranular insular, and entorhinal cortices, the ventral subiculum of the hippocampus, dorsal tenia tecta, claustrum, lateral septum, dorsal striatum, nucleus accumbens (core and shell), olfactory tubercle, bed nucleus of stria terminalis (BST), medial, central, cortical, and basal nuclei of amygdala, and the suprachiasmatic, arcuate, and dorsomedial nuclei of the hypothalamus. The posterior PV distributes more heavily than the anterior PV to the dorsal striatum and to the central and basal nuclei of amygdala. PT projections significantly overlap with those of PV, with some important differences. PT distributes less heavily than PV to BST and to the amygdala, but much more densely to the medial prefrontal and entorhinal cortices and to the ventral subiculum of hippocampus. As described herein, PV/PT receive a vast array of afferents from the brainstem, hypothalamus, and limbic forebrain, related to arousal and attentive states of the animal, and would appear to channel that information to structures of the limbic forebrain in the selection of appropriate responses to changing environmental conditions. Depending on the specific complement of emotionally associated information reaching PV/PT at any one time, PV/PT would appear positioned, by actions on the limbic forebrain, to direct behavior toward a particular outcome over a range of outcomes.
    The Journal of Comparative Neurology 06/2008; 508(2):212-37. · 3.66 Impact Factor
  • Walter B Hoover, Robert P Vertes
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    ABSTRACT: The medial prefrontal cortex (mPFC) has been associated with diverse functions including attentional processes, visceromotor activity, decision making, goal directed behavior, and working memory. Using retrograde tracing techniques, we examined, compared, and contrasted afferent projections to the four divisions of the mPFC in the rat: the medial (frontal) agranular (AGm), anterior cingulate (AC), prelimbic (PL), and infralimbic (IL) cortices. Each division of the mPFC receives a unique set of afferent projections. There is a shift dorsoventrally along the mPFC from predominantly sensorimotor input to the dorsal mPFC (AGm and dorsal AC) to primarily 'limbic' input to the ventral mPFC (PL and IL). The AGm and dorsal AC receive afferent projections from widespread areas of the cortex (and associated thalamic nuclei) representing all sensory modalities. This information is presumably integrated at, and utilized by, the dorsal mPFC in goal directed actions. In contrast with the dorsal mPFC, the ventral mPFC receives significantly less cortical input overall and afferents from limbic as opposed to sensorimotor regions of cortex. The main sources of afferent projections to PL/IL are from the orbitomedial prefrontal, agranular insular, perirhinal and entorhinal cortices, the hippocampus, the claustrum, the medial basal forebrain, the basal nuclei of amygdala, the midline thalamus and monoaminergic nuclei of the brainstem. With a few exceptions, there are few projections from the hypothalamus to the dorsal or ventral mPFC. Accordingly, subcortical limbic information mainly reaches the mPFC via the midline thalamus and basal nuclei of amygdala. As discussed herein, based on patterns of afferent (as well as efferent) projections, PL is positioned to serve a direct role in cognitive functions homologous to dorsolateral PFC of primates, whereas IL appears to represent a visceromotor center homologous to the orbitomedial PFC of primates.
    Brain Structure and Function 10/2007; 212(2):149-79. · 7.84 Impact Factor
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    ABSTRACT: The medial prefrontal cortex and the hippocampus serve well recognized roles in memory processing. The hippocampus projects densely to, and exerts strong excitatory actions on, the medial prefrontal cortex. Interestingly, the medial prefrontal cortex, in rats and other species, has no direct return projections to the hippocampus, and few projections to parahippocampal structures including the entorhinal cortex. It is well established that the nucleus reuniens of the midline thalamus is the major source of thalamic afferents to the hippocampus. Since the medial prefrontal cortex also distributes to nucleus reuniens, we examined medial prefrontal connections with populations of nucleus reuniens neurons projecting to hippocampus. We used a combined anterograde and retrograde tracing procedure at the light and electron microscopic levels. Specifically, we made Phaseolus vulgaris-leuccoagglutinin (PHA-L) injections into the medial prefrontal cortex and Fluorogold injections into the hippocampus (CA1/subiculum) and examined termination patterns of anterogradely PHA-L labeled fibers on retrogradely FG labeled cells of nucleus reuniens. At the light microscopic level, we showed that fibers from the medial prefrontal cortex form multiple putative synaptic contacts with dendrites of hippocampally projecting neurons throughout the extent of nucleus reuniens. At ultrastructural level, we showed that medial prefrontal cortical fibers form asymmetric contacts predominantly with dendritic shafts of hippocampally projecting reuniens cells. These findings indicate that nucleus reuniens represents a critical link between the medial prefrontal cortex and the hippocampus. We discuss the possibility that nucleus reuniens gates the flow of information between the medial prefrontal cortex and hippocampus dependent upon attentive/arousal states of the organism.
    Brain Research Bulletin 04/2007; 71(6):601-9. · 2.94 Impact Factor
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    ABSTRACT: The nucleus reuniens (RE) is the largest of the midline nuclei of the thalamus and exerts strong excitatory actions on the hippocampus and medial prefrontal cortex. Although RE projections to the hippocampus have been well documented, no study using modern tracers has examined the totality of RE projections. With the anterograde anatomical tracer Phaseolus vulgaris leuccoagglutinin, we examined the efferent projections of RE as well as those of the rhomboid nucleus (RH) located dorsal to RE. Control injections were made in the central medial nucleus (CEM) of the thalamus. We showed that the output of RE is almost entirely directed to the hippocampus and "limbic" cortical structures. Specifically, RE projects strongly to the medial frontal polar, anterior piriform, medial and ventral orbital, anterior cingulate, prelimbic, infralimbic, insular, perirhinal, and entorhinal cortices as well as to CA1, dorsal and ventral subiculum, and parasubiculum of the hippocampus. RH distributes more widely than RE, that is, to several RE targets but also significantly to regions of motor, somatosensory, posterior parietal, retrosplenial, temporal, and occipital cortices; to nucleus accumbens; and to the basolateral nucleus of amygdala. The ventral midline thalamus is positioned to exert significant control over fairly widespread regions of the cortex (limbic, sensory, motor), hippocampus, dorsal and ventral striatum, and basal nuclei of the amygdala, possibly to coordinate limbic and sensorimotor functions. We suggest that RE/RH may represent an important conduit in the exchange of information between subcortical-cortical and cortical-cortical limbic structures potentially involved in the selection of appropriate responses to specific and changing sets of environmental conditions.
    The Journal of Comparative Neurology 01/2007; 499(5):768-96. · 3.66 Impact Factor
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    ABSTRACT: The theta rhythm is the largest extracellular synchronous signal that can be recorded from the mammalian brain and has been strongly implicated in mnemonic processes of the hippocampus. We describe (a) ascending brain stem-forebrain systems involved in controlling theta and nontheta (desynchronization) states of the hippocampal electroencephalogram; (b) theta rhythmically discharging cells in several structures of Papez's circuit and their possible functional significance, specifically with respect to head direction cells in this same circuit; and (c) the role of nucleus reuniens of the thalamus as a major interface between the medial prefrontal cortex and hippocampus and as a prominent source of afferent limbic information to the hippocampus. We suggest that the hippocampus receives two main types of input: theta rhythm from ascending brain stem- diencephaloseptal systems and information bearing mainly from thalamocortical/cortical systems. The temporal convergence of activity of these two systems results in the encoding of information in the hippocampus, primarily reaching it from the entorhinal cortex and nucleus reuniens.
    Behavioral and Cognitive Neuroscience Reviews 10/2004; 3(3):173-200.