Publications (49) View all
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Article: Postnatal development of layer III pyramidal cells in the primary visual, inferior temporal, and prefrontal cortices of the marmoset
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ABSTRACT: Abnormalities in the processes of the generation and/or pruning of dendritic spines have been implicated in several mental disorders including autism and schizophrenia. We have chosen to examine the common marmoset (Callithrix jacchus) as a primate model to explore the processes. As a first step, we studied the postnatal development of basal dendritic trees and spines of layer-III pyramidal cells in the primary visual sensory cortex (V1), a visual association cortex (inferior temporal area, TE), and a prefrontal cortex (area 12, PFC). Basal dendrites in all three areas were longer in adulthood compared with those in the newborn. In particular, rapid dendritic growth occurred in both TE and PFC around the second postnatal month. This early growth spurt resulted in much larger dendritic arbors in TE and PFC than in V1. The density of the spines along the dendrites peaked at 3 months of age and declined afterwards in all three areas: the degree of spine pruning being greater in V1 than in TE and PFC. The estimates of the total numbers of spines in the basal dendrites of a single pyramidal cell were larger in TE and PFC than in V1 throughout development and peaked around 3 months after birth in all three areas. These developmental profiles of spines and dendrites will help in determining assay points for the screening of molecules involved in spinogenesis and pruning in the marmoset cortex.Frontiers in Neural Circuits 03/2013; 7:31. · 5.10 Impact Factor -
Article: Distribution and progression of amyloid-beta deposits in the amygdala of the aged macaque monkey, and parallels with zinc distribution.
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ABSTRACT: In this study, we have mapped amyloid beta (Abeta) deposition in the amygdala of five aged Japanese monkeys (from 23 to 30 years old). In brief, the aged monkey amygdala shows a topographic distribution of Abeta deposits that is subnucleus specific and exhibits a distinct temporal progression. The pattern is similar to the distribution of Abeta deposits in the human amygdala of Alzheimer's patients and of high plaque nondemented cases. The spatial distribution and temporal progression were correlated with the distribution of free zinc (Zn), which is known to mediate Abeta aggregation. For the basolateral group of subnuclei in particular, there is a clear dorsoventral gradient in the progressive distribution of Abeta. Abeta depositions first appear in the ventral division of the lateral nucleus and parvicellular division of the accessory basal nucleus, and then extend into the ventral part of the basal and paralaminar nuclei. All these nuclei are also Zn-dense. Conversely, Zn-weak nuclei, which are more dorsally situated (i.e. dorsal division of lateral nucleus and magnocellular division of basal nucleus) showed only a low level of Abeta deposits, even in brains with the greatest Abeta burden. In contrast to the basolateral group, the central and medial nuclei and cortical group had Abeta deposits only at later stages. In the central and medial nuclei, we identified a lateromedial gradient of Abeta deposits, again similar to the gradient of Zn-distribution. In the cortical group, Abeta deposits are densest in the deep layer, where Zn is also densest. Thus, we suggest the macaque amygdala, with its clear topographic distribution of Abeta deposits, may be an effective model for examining the complex mechanisms of vulnerability to Abeta deposits. A primate model would be advantageous for experimental interventions geared toward therapeutic protection from Alzheimer's disease, including by microarray analysis and genetic manipulation.Neuroscience 05/2009; 159(4):1374-83. · 3.38 Impact Factor -
Article: Comparative analysis of layer-specific genes in Mammalian neocortex
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ABSTRACT: We examined the expression patterns of 4 layer-specific genes in monkey and mouse cortices by fluorescence double in situ hybridization. Based on their coexpression profiles, we were able to distinguish several subpopulations of deep layer neurons. One group was characterized by the expression of ER81 and the lack of Nurr1 mRNAs and mainly localized to layer 5. In monkeys, this neuronal group was further subdivided by 5-HT2C receptor mRNA expression. The 5-HT2C(+)/ER81(+) neurons were located in layer 5B in most cortical areas, but they intruded layer 6 in the primary visual area (V1). Another group of neurons, in monkey layer 6, was characterized by Nurr1 mRNA expression and was further subdivided as Nurr1(+)/connective tissue growth factor (CTGF)(-) and Nurr1(+)/CTGF(+) neurons in layers 6A and 6B, respectively. The Nurr1(+)/CTGF(+) neurons coexpressed ER81 mRNA in monkeys but not in mice. On the basis of tracer injections in 3 monkeys, we found that the Nurr1(+) neurons in layer 6A send some corticocortical, but not corticopulvinar, projections. Although the Nurr1(+)/CTGF(-) neurons were restricted to lateral regions in the mouse cortex, they were present throughout the monkey cortex. Thus, an architectonic heterogeneity across areas and species was revealed for the neuronal subpopulations with distinct gene expression profilesCereb.Cortex. 08/2007; 17(8). -
Article: Zinc-rich transient vertical modules in the rat retrosplenial cortex during postnatal development.
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ABSTRACT: The rat retrosplenial cortex is part of a heavily interconnected limbic circuit, considered to have an important role in spatial memory. Interestingly, the granular retrosplenial cortex has an exceptionally distinct system of dendritic bundles, originating from callosally projecting pyramidal neurons in layer II. These can be detected as early as postnatal day 5; and, although their functional significance remains to be elucidated, the existence of these bundles makes the granular retrosplenial cortex an attractive model system for a wide range of development and functional investigations. Here, we report four results concerning the development of modularity in the granular retrosplenial cortex in rats as investigated by neurochemical markers associated to cortico-cortical and thalamo-cortical connections. Emphasis is placed on zinc, an activity-related substance associated with glutamatergic, non-thalamic terminations. 1) Zinc shows a transient strong expression during early postnatal development, but later than the appearance of the upper layer bundles (at postnatal day 5). By postnatal day 11 to postnatal day 15 staining for zinc achieved its most complex pattern; such that layer I had an elaborate organization both in the tangential and radial dimensions. Three sublaminae were distinguished (layers Ia-c): a superficial, thin tier (Ia) with patchy, moderate staining which periodically intruded into the underlying layer Ib ("funnel" modules), a middle band of variable width and light staining (Ib), and a deep, thin band with heavy and patchy staining (Ic) which, at rostral levels, spread upward into layer Ib (as "dome-like" modules). 2) At postnatal day 15, immunohistochemical methods showed that layers Ia, b zinc-funnels were co-localized with glutamate receptor subunits 2/3, GABA receptor type A alpha1 subunit and the thalamo-cortical marker, vesicular glutamate transporter 2. Layer Ic and the zinc dome-like modules were co-labeled for the cortico-cortical marker, vesicular glutamate transporter 1 and calretinin. 3) The spatial coincidence between zinc funnels in layers Ia, b and vesicular glutamate transporter 2 was further investigated by electron microscopy, which demonstrated co-localization of zinc and vesicular glutamate transporter 2 in synaptic boutons. The unusual co-localization of zinc and thalamo-cortical terminations was confirmed by retrograde transport of zinc to neurones in the anterodorsal thalamic nucleus at postnatal day 9 and postnatal day 13, and can thus be considered a transient zinc expression in thalamo-cortical boutons. This was not observed at postnatal day 28 or later. 4) After postnatal day 18, zinc staining started to fade in all layers. Before postnatal day 21, the heavy staining for zinc in the domes had completely disappeared. Zinc staining in layer Ia and the funnels virtually disappeared after postnatal day 28. A transient expression of zinc is reported in at least one other cortical area (layer IV of barrel cortex from postnatal day 5 to postnatal day 14, maximal at postnatal days 9-11). We conclude that the transient expression of zinc can occur in both limbic and sensory areas, and that down-regulation of zinc in cortical modules might be related to synaptic plasticity and remodeling during development.Neuroscience 02/2006; 138(2):523-35. · 3.38 Impact Factor -
Article: Transgenic mice expressing a fluorescent in vivo label in a distinct subpopulation of neocortical layer 5 pyramidal cells
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ABSTRACT: The neuronal components of cortical circuits have been characterized on the basis of their morphological and functional properties, and further refined by correlation of marker proteins with particular cell types. This latter approach has been very fruitful for GABA-containing neurons, but comparable diagnostic markers for subpopulations of excitatory pyramidal cells have been more elusive. An emerging new approach consists of transgenic mice that express fluorescent proteins under the control of promoters that are active in specific cell types. Here, we analyzed a line of transgenic mice that carries a transgene consisting of regulatory sequences of the potassium channel Kv3.1 and enhanced yellow fluorescent protein (EYFP). In these mice, a set of neurons in neocortical layer 5 expresses high levels of the transgenic marker protein. EYFP-expressing, and nonexpressing layer 5 cells were easily identified in living tissue under conditions suitable for patch-clamp electrophysiology. By using immunolabeling, retrograde Fast Blue labeling and electrophysiological recordings with biocytin injections, we identified the fluorescent neurons as a population of pyramidal cells with distinct morphological and electrophysiological properties when compared with nonfluorescent neighboring layer 5 pyramidal cells. The most prominent morphological difference between these two populations was a much smaller number of apical oblique dendrites in EYFP-positive as compared with the EYFP-negative cells. The most prominent electrophysiological feature was a steady spike frequency adaptation in EYFP-positive cells, whereas EYFP-negative cells responded to a depolarizing current injection with a closely spaced spike doublet followed by constant frequency firing. The in vivo labeled transgenic mice provide an experimental tool for further functional differentiation of these populations of layer 5 pyramidal cellsJ.Comp Neurol. 11/2004; 480(1).
