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DISC1 immunoreactivity at the light and ultrastructural level in the human neocortex.

Disrupted-In-Schizophrenia 1 (DISC1) is one of two genes that straddle the chromosome 1 breakpoint of a translocation associated with an increased risk of schizophrenia. DISC1 has been identified in the brain of various mammalian species, but no previous immunocytochemical studies have been conducted in human neocortex. We examined DISC1 immunoreactivity in frontal and parietal cortex (BA 4, 9, 39, and 46) in normal human brain. At the light microscopic level, immunolabeling was prominent in the neuropil, in multiple populations of cells, and in the white matter. At the ultrastructural level, staining was prominent in structures associated with synaptic function. Immunolabeled axon terminals comprised 8% of all terminals and formed both asymmetric and symmetric synapses. Labeled axon terminals formed synapses with labeled spines and dendrites; in some, only the postsynaptic density (PSD) of the postsynaptic structure was labeled. The most common configuration, however, was an unlabeled axon terminal forming an asymmetric synapse with a spine that had immunoreactivity deposited on the PSD and throughout the spine. The presence of DISC1 in multiple types of synapses suggests the involvement of DISC1 in corticocortical as well as thalamocortical connections. Staining was also present in ribosomes, parts of the chromatin, in dendritic shafts, and on some microtubules. Labeling was absent from the Golgi apparatus and multivesicular bodies, which are associated with protein excretion. These anatomical localization data suggest that DISC1 participates in synaptic activity and microtubule function, and are consistent with the limited data on its adult function.

Adult↗

Architectonic map of neocortex of the normal mouse.

The neocortex of the normal mouse has been subdivided into architectonic fields on the basis of its cellular and fiber patterns. The map of medial, retrohippocampal, frontal and insular regions is little different from that of Brodmann as modified in minor ways by Krieg. The map of parietal, occipital and temporal regions follows closely the major rearrangements introduced to Brodmann's map by Krieg. Krieg's map has been modified to give individual status to the barrel fields and to disignate occipital fields around the full circumference of field 17, and temporal fields circumferentially around field 41.

Animals↗

Receptive fields of barrels in the somatosensory neocortex of the rat.

Peripheral receptive fields of "barrels" in the somatosensory neocortex (SmI) of rats were determined with microelectrope recording and anatomical techniques. A method of flattening each hemisphere prior to embedding was devised so that the organization of layer IV could be seen through the full extent of SmI on a single section. All of the barrels in the rat are located within layer IV of Smi. sinus hairs on the lateral and rostral face and furry buccal pad project to a continuous sheet of barrels in the head area of the contralateral SmI. The pattern of projections in this area indicates that each barrel receives information from one sinus hair. Large whisking vibrissae project to the largest cell-dense barrels and smaller non-whisking sinus hairs project to smaller barrels that are relatively cell-sparse. Barrels were also found outside of the head area in regions that receive projections from the forepaw and hindfoot. Receptive fields of these barrels are located on glabrous and hairy surfaces of the appendages that do not include any sinus hairs. Other parts of the body project to cell-dense areas of SmI that do not appear to contain barrels. Barrel subgroups and other somatotopic areas are separated by narrow barrel-free zones. As a result of this pattern of contrasting cell densities, an outline of the rat's body is delineated within layer IV.

Animals↗

Somatotopic organization of mechanosensory projections to SII cerebral neocortex in the raccoon (Procyon lotor).

The pattern of projections of peripheral receptors to the neocortex in the second somesthetic receiving area (SII) was mapped in raccoons. The purpose was to determine if the projection area of peripheral receptors to the forepaw area in the SII region is disproportionally enlarged as it is in SI. Tungsten microelectrode recording procedures were used to map thoroughly the inferior wall of the suprasylvian sulcus for regions responsive to mechanical stimulation of peripheral receptors. The results show that: 1. The forepaw area in SII shows an enlargement commensurate with that found in the SI. This suggests that those factors that are selective for tactile acuity of the raccoon forepaw were operating in the evolution of SII as they were in SI. 2. The somatotopic organization of mechanoreceptive projections to SII is reversed mediolaterally compared to previous descriptions of this arrangement in other mammals: projections form axial structures lie medially and those from apical structures lie laterally along the inferior bank of the suprasylvian sulcus in the raccoon.

Animals↗

Determinants of cell shape and orientation: a comparative Golgi analysis of cell-axon interrelationships in the developing neocortex of normal and reeler mice.

Patterns of dendritic development in the neocortex of normal and reeler E15-17 mouse embryos are studied in Golgi impregnations. Interactions between dendrites and axon-rich strata appear to be critical determinants of dendritic morphology in both genotypes. Firstly, axon-dendrite proximity appears to stimulate dendritic sprouting, elongation and branching. Secondly, the position of the axon-rich strata with respect to the differentiating cell appears to determine the direction of dendritic growth and thereby the ultimate configuration of the dendritic arbor. With regard to specific cell configurations, a multipolar form is generated when the cell is embedded in an axon-rich zone. A monopolar or bipolar configuration is achieved when the cell lies in the axon-poor cortical plate and addresses and axon-rich stratum with one or both radially extended migratory processes. Such variations in the configuration of neurons with polar dendritic systems may be observed uniquely in the mutant cortex because axon-rich zones are stratified anomalously at multiple levels in the cortical plate. As a consequence, polar dendritic systems develop from either the superior, the inferior or both somatic poles of postmigratory cells. Pyramidal cells may, therefore, develop a normal upright or an abnormal "upside-down" disposition. Regardless of the orientation of the polar dendritic system, the axon emerges from the inferior aspect of the cell suggesting that there has been no rotation of the original migratory axis of the cell.

Afferent Pathways↗

Tangential organization of thalamic projections to the neocortex in the mouse.

Using the anterograde degeneration technique, we examine the tangential organization of a thalamofugal axon population (class I of Frost and Caviness, '80) whose terminations are preferentially distributed to the middle tier (located in layers III and/or IV) of three radially separated tiers of thalamic projections to the neocortex. Less extensive data are also presented on the tangential organization of thalamofugal axon populations (class II of Frost and Caviness, '80) that do not terminate preferentially in the middle tier, but that are otherwise heterogeneous with respect to their radial pattern of intracortical termination. The projections of class I axons are distributed to all neocortical fields with the possible exception of fields 13,25, and 35. The class I projections to a given cortical field (with the possible exception of the cortex of the second somatosensory representation) originate in only one thalamic nucleus. The class I projections of an individual thalamic nucleus form a cortical representation of the nucleus that constitutes a "first order line-to-line" (topologic) transformation of the nuclear volume. The ensemble of class I projections forms a cortical representation of the corresponding thalamic regions that constitutes a "second order line-to-line" (non-topologic) transformation of the thalamic volume. Class II axons project to all neocortical fields. Classs II and class I projections contrast in that the class II projections of multiple thalamic nuclei overlap in the tangential plane of any given sector of the cortex. While the class II projections of the intralaminar nuclei and the widely projecting ventromedial nucleus are known to be topologically organized, the tangential organization of class II projections arising in other nuclei is incompletely understood.

Afferent Pathways↗

Radial organization of thalamic projections to the neocortex in the mouse.

The intracortical distributions of the thalamic projections to a large number of neocortical fields are studied by the anterograde degeneration methods in the mouse. The basic radial distribution of terminating thalamofugal axons is uniform throughout the mouse cortex and is essentially the same as that encountered in other mammalian species. Terminating axons are concentrated in three tiers: an outer tier in layer I, a middle tier in layers IV and/or III, and an inner tier in layer VI. In most fields, terminating axons also extend, to some extent, into layer V. Variations are encountered from field to field, particularly in the density and degree of divergence of projections and in the radial extent of individual tiers with respect to cytoarchitectonic layers. In accord with other studies, the thalamic projections to each field appear to be composed of two general axon classes. Class I axons terminate densely in the middle tier, seem to be of large caliber, and often have collaterals to the other tiers. Class II axons do not terminate densely in the middle tier and seem to be of small caliber. Terminating class II axons may be distributed to one or more tiers and may be concentrated in the inner and/or outer tiers. The thalamic projection to each field has its origin in multiple nuclei. All thalamic nuclei projecting to the neocortex appear to have class II projections and many also have class I projections. Patterns of degeneration in the cortex associated with lesions in different positions in many nuclei suggest that thalamic relay neurons are organized along "lines of projection"--neurons in the same line projecting to the same tangentially restricted cortical region. The neurons of origin of class I and class II axons are intermixed along the lines of projection.

Afferent Pathways↗

Topographic analysis of the innervation of the rat neocortex and hippocampus by the basal forebrain cholinergic system.

The basal forebrain-cortex connections of the rat were topographically mapped by retrograde tracer methods; and their contribution to the cholinergic innervation of the cortex was assessed by excitotoxin lesions placed in the rostral and caudal aspects of the complex. Discrete injections of tracer into frontal cortex labeled the prominent multipolar acetylcholinesterase (AchE)-positive cells of the ventromedial globus pallidus. Injections of tracer into the parietal cortex labelled cells in the ventral globus pallidus, the underlying substantia innominata, and the lateral hypothalamus. Separate injections of Fast Blue and Nuclear Yellow in the frontal and in the parietal cortex resulted in double-labeled cells in the ventral globus pallidus, which indicates that at least some of these cells may possess collateralizing axons. The cingulate cortex is innervated predominantly by neurons in the nucleus of the horizontal limb of the diagonal band. The occipital cortex was also shown to receive a projection primarily from the nucleus of the horizontal limb of the diagonal band. The hippocampal formation is innervated primarily by cells located in the vertical limb of the diagonal band and in the medial septum. Consistent with the results of the retrograde tracing studies, excitotoxin lesions affecting the diagonal band and medial septum decreased choline acetyltransferase (CAT) activity up to 40% on the occipital cortex and by 64% in the hippocampus, but did not affect CAT activity in the rostral neocortex. In contrast, ibotenate lesions of the caudal ventral globus pallidus and substantia innominata caused decreases in CAT activity in the frontal cortex of up to 65% without affecting enzyme activity in the hippocampal formation. The results of the present study provide details on the topographic organization of the cortical projections originating in the basal forebrain complex and indicate that these neurons are the predominant source of cortical cholinergic innervation.

Acetylcholine↗

Callosal connections of the posterior neocortex in normal-eyed, congenitally anophthalmic, and neonatally enucleated mice.

Following multiple injections of horseradish peroxidase into the posterior neocortex of one hemisphere, we examined the distribution of retrogradely labeled cells and anterogradely labeled terminations in tangential and coronal sections through contralateral areas 17 and 18 in three groups of adult mice: normal-eyed (ZRDCT-n and C57Bl/6J strains), congenitally anophthalmic (ZRDCT-an strain), neonatally enucleated (ZRDCT-n strain). In agreement with previous studies, we observed that the pattern of callosal connections in areas 17 and 18 of normal-eyed mice contains the following features: (1) a dense band of callosal cells and terminations separating the interiors of areas 17 and 18, which have relatively few callosal connections, (2) a ring-like configuration anterolateral to area 17, (3) a region of dense labeling lateral to area 18, (4) a narrow band of labeling bridging the posterior portion of area 18, and (5) a region of labeling anteromedial to area 17. We find that all these features of the normal callosal pattern are recognizable in congenitally anophthalmic mice. Their presence in mice that never had eyes supports the hypothesis that central visual pathways can develop many aspects of their connectivity in the absence of input from the periphery. However, we also find that the details of certain features of the callosal pattern in congenitally eyeless mice often differ from those of the same features in normal-eyed mice, and that the between-animal variability in the appearance of these features is higher in eyeless mice. These latter findings indicate that the eyes are needed during normal development to fine-tune the pattern of callosal connections. Our results also reveal that the callosal pattern in neonatally enucleated mice does not differ significantly from that in congenitally anophthalmic mice, indicating that the period in which the eyes guide callosal development extends into postnatal life. While the present data do not delineate the time course of this period, the finding of similarly abnormal callosal patterns in congenitally anophthalmic and neonatally enucleated mice suggests that the eyes exert little if any influence prenatally. Finally, examination of coronal sections indicates that the laminar distribution of callosal connections develops normally in both groups of eyeless mice.

Animals↗

Ultrastructural organization of choline-acetyltransferase-immunoreactive fibres innervating the neocortex from embryonic ventral forebrain grafts.

Suspension grafts of foetal tissue rich in cholinergic neurones were transplanted into the frontoparietal cortex of rats that had previously undergone deafferentation of the extrinsic cholinergic innervation of the cortex by injection of ibotenic acid into the nucleus basalis magnocellularis. The cortical tissue containing the graft was processed for electron microscopic immunocytochemistry by using a monoclonal antibody to choline acetyltransferase (ChAT) in order to examine the contacts established between cholinergic fibres from the graft and the host neocortex. The density, distribution, and targets of this graft-host innervation were compared with those seen in the intact and deafferented cortex. ChAT-positive fibres in both grafted and control animals formed extensive synaptic connections with various cortical neural elements--those of graft origin being of similar morphology to those in the intact cortex. However, the distribution of postsynaptic cortical targets of the graft-derived ChAT-immunoreactive boutons was abnormal, such that a greater percentage of such terminals formed synaptic contacts with neuronal perikarya, especially layer V pyramidal neurones, than was seen in control brains. It is possible that the formation of new synaptic contacts between the embryonic graft and host frontoparietal cortex may, in part, be necessary for the restoration of functional activity that has been previously reported in these grafted animals.

Animals↗

Development of projections from somatic motor-sensory areas of neocortex to the diencephalon and brainstem in the North American opossum.

The development of projections from somatic motor-sensory areas of neocortex to the diencephalon and brainstem was studied by using the orthograde transport of wheat germ agglutinin conjugated to horseradish peroxidase (WGA-HRP) in a series of pouch-young opossums. The opossum was chosen for study because it is born in a very immature state, 12 days after conception, and has a protracted postnatal development. Cortical axons form a cerebral peduncle by at least postnatal day (PD) 10, a medullary pyramid by estimated PD (EPD) 17, a pyramidal decussation by EPD 26, and reach the first cervical segment of the spinal cord by EPD 29. Cortical axons innervate diencephalic nuclei and perhaps the substantia nigra by EPD 17, but do not grow into more caudal brainstem nuclei until EPD 26. The first brainstem areas innervated by cortical axons are the mesencephalic and rostral pontine tegmentum and parts of the pontine gray adjacent to the pyramidal tract (EPD 29). By EPD 31, cortical axons project to additional areas of the pontine gray, the gigantocellular reticular formation, the medial accessory olive, and the cuneate nucleus. Cortical innervation of the red nucleus and superior colliculus begins at EPD 31 but is not well developed until EPD 35. Cortical axons do not innervate the parvicellular reticular formation or the sensory trigeminal nuclei until EPD 35. Evidence for transient cerebrocerebellar axons was also found.

Animals↗

Monoclonal antibodies to the turtle cortex reveal neuronal subsets, antigenic cross-reactivity with the mammalian neocortex, and forebrain structures sharing a pallial derivation.

The dorsal cortex of the pond turtle (Pseudemys scripta) is a relatively simple structure consisting of two principal classes of neurons that occupy three distinct layers. Morphological, pharmacological, and physiological data suggest many similarities to the mammalian neocortex, rendering it an interesting preparation for comparative studies. We prepared monoclonal antibodies to the turtle dorsal cortex by immunizing mice with cortical tissue from adult turtles. Twelve antibodies were generated that recognize specific components of the turtle cortex. Among these, eight antibodies label only neurons and four label only ependymal glial cells. Differences in tissue staining pattern and immunoglobulin class suggest a heterogeneity of antigenic specificity among the antibodies. The staining patterns of three of our antibodies are described. TC3, like all other neuron-marking antibodies generated, labels a subset of both pyramidal and stellate cell types. It also cross-reacts with a subset of mammalian cortical neurons and labels them with a pattern similar to that observed in the turtle cortex. TC5 stains ependymal cells and their glial processes in the turtle cortex, and cross-reacts with fibrous astrocytelike processes in mammalian neocortical white matter. TC9 appears to recognize antigens of neurons sharing a pallial derivation in turtle.

Animals↗

Topography of interhemispheric connections in neocortex of mice with congenital deficiencies of the callosal commissure.

Normally, axons within the corpus callosum are ordered according to the cortical regions from which they originate, and callosal cells and terminations form elaborate cortical patterns related to the underlying topographic representations of the sensory periphery. About 30% of mice of the BALB/c strain show congenital deficiencies of the callosal commissure which range from total absence of the corpus callosum to a moderate reduction in the size of this commissure. In the light of current theories about the origin of these callosal deficiencies, it seems likely that fibers crossing the midplane in mutant mice have to circumvent local disturbances along their migration path. Since these disturbances in fiber trajectory may, in turn, alter the overall pattern of callosal projections, we set out to investigate whether the distribution of callosal connections in mice with marked deficiencies of the corpus callosum is as ordered as in normal mice. In groups of normal and mutant mice, we used multiple injections of horseradish peroxidase to reveal the overall distribution of callosal connections and restricted injections of horseradish peroxidase conjugated with wheat germ agglutinin to reveal finer aspects of the organization of the callosal pathway in these animals. Our results show that the number of labeled cells is reduced in mice with a small corpus callosum and that no labeled cells are present in the neocortex of acallosal mice. Furthermore, the topographic distribution of fibers within the corpus callosum of mutant mice can be significantly less ordered than in normal mice. However, even in mice with extreme deficiencies of the corpus callosum, callosal fibers originate from and terminate in all major areas of the cortex, and, within these areas, callosal cells and terminations are distributed according to the normal plan. The laminar distribution of callosal cells also appears normal in these mice. These findings indicate that gross developmental anomalies of the corpus callosum do not prevent normal specification of the callosal pattern during development. Within the context of current theories about the origin of congenital callosal deficiencies, our findings suggest that callosal fibers are able to establish appropriate contralateral connections in spite of alterations of their migration route. They also suggest that fiber topography within the corpus callosum does not play an important role in guiding migrating axons to their correct contralateral targets. Finally, our failure to find labeled fibers within the anterior commissure indicates that this commissure does not serve as an alternative route for deviated callosal axons.

Agenesis of Corpus Callosum↗

GABA-immunoreactive synaptic boutons in the rat basal forebrain: comparison of neurons that project to the neocortex with pallidosubthalamic neurons.

Although the basal forebrain, including the globus pallidus, contains a high concentration of gamma-aminobutyric acid (GABA), it is not known whether all types of neuron in the globus pallidus receive GABAergic synaptic input. We have studied two types of neuron: typical pallidal neurons that project to the subthalamic nucleus and magnocellular neurons which are found in the medial and ventral borders of the globus and project to the sensorimotor cortex. The postembedding immunogold staining of endogenous GABA revealed many preterminal axons and synaptic boutons that contained GABA immunoreactivity. Neurons that projected to the neocortex were postsynaptic to some of the GABA-immunoreactive boutons, the majority of which formed symmetrical membrane specializations. From a series of random electron micrographs through the perikarya and proximal dendrites of such retrogradely labelled neurons the density of GABA-containing afferent synaptic boutons was estimated to be 0.58 GABA-containing boutons per 100 micron of neuronal membrane. The GABA-containing boutons accounted for 72% of the total afferent input in the proximal regions of the pallidocortical neurons examined. The pallidosubthalamic neurons received many more afferent boutons than did the cortically projecting neurons, a high proportion (80.4%) of which were immunoreactive for GABA. The density of GABA-containing boutons in contact with pallidosubthalamic neurons was 8.9 boutons per 100 micron. It is concluded that cortically projecting basal forebrain neurons, that are probably cholinergic, are innervated by GABA-containing afferent boutons. However, pallidosubthalamic neurons in the same part of the basal forebrain are much more densely innervated by GABA-containing boutons.

Animals↗

Multiple types of neuropeptide Y-containing neurons in primate neocortex.

The avidin-biotin-peroxidase method was used at the light and electron microscopic levels to analyze neuropeptide Y (NPY)-containing neurons in the neocortex of six adult macaque monkeys. Regions studied included various sensory, motor, limbic, and association areas, designated as 17, 18, 7, 22, 3, 4, 6, 24, and 9 by Brodmann (Beiträge zur Histologischen Lokalisation der Grosshirnrinde. Leipzig: Barth, '06). Several types of NPY-containing neurons can be distinguished by their laminar location, by the size of their perikarya, and by the size, shape, and pattern of ramification of their processes: 1) layer I small local circuit neurons; 2) layer II granule cells; 3) aspiny stellate cells located in layers II-III and V-VI, with long, slender dendrites; 4) sparsely spiny stellate cells; 5) aspiny stellate cells with long, horizontally oriented dendrites, whose cell body is situated in layer VI; 6) Martinotti cells in areas 9, 7, and 24; and 7) multipolar neurons situated in the white matter subjacent to the cortical gray. The possibility of additional neuronal types containing NPY is suggested by labeled densely spinous dendrites in area 6 and recurving axons and axonal loops in the supragranular layers in areas 7 and 9. No NPY-containing neurons were found in layer IV of any area, except layers IVA and B of the visual cortex. Likewise, nonneuronal elements were not labeled. The regional differences in the distribution of some NPY-containing neuron types may reflect adaptations of local neuronal circuits for specialized functions.

Animals↗

Monoclonal antibody to neurofilament protein (SMI-32) labels a subpopulation of pyramidal neurons in the human and monkey neocortex.

A monoclonal antibody that recognizes a nonphosphorylated epitope on the 168 kDa and 200 kDa subunits of neurofilament proteins has been used in an immunohistochemical study of cynomolgus monkey (Macaca fascicularis) and human neocortex. This antibody, SMI-32, primarily labels the cell body and dendrites of a subset of pyramidal neurons in both species. A greater proportion of neocortical pyramidal neurons were SMI-32 immunoreactive (ir) in the human than in the monkey. SMI-32-ir neurons exhibited consistent differences in the intensity of their immunoreactivity that correlated with cell size. The cellular specificity of SMI-32 immunoreactivity suggests that a subpopulation of neurons can be distinguished on the basis of differences in the molecular characteristics of basic cytoskeletal elements such as neurofilament proteins. The size, density, and laminar distribution of SMI-32-ir neurons differed substantially across neocortical areas within each species and between species. Differences across cortical areas were particularly striking in the monkey. For example, the anterior parainsular cortex had a substantial population of large SMI-32-ir neurons in layer V and a near absence of any immunoreactive neurons in the supragranular layers. This contrasted with the cortical area located more laterally on the superior temporal gyrus, where layers III and V contained substantial populations of large SMI-32-ir neurons. Both areas differed significantly from the posterior inferior temporal gyrus, which was distinguished by a bimodal distribution of large SMI-32-ir neurons in layer III. Differences across human areas were less obvious because of the increase in the number of SMI-32-ir neurons. Perhaps the most notable differences across human areas resulted from shifts in the density of the larger SMI-32-ir neurons in deep layer III. A comparison between the species revealed that isocortical areas exhibited greater differences in their representation of SMI-32-ir neurons than primary sensory or transitional cortical areas. A comparison of distribution patterns of SMI-32-ir neurons across monkey cortical areas and data available on the laminar organization of cortical efferent neurons suggests that a common anatomic characteristic of this chemically identified subpopulation of neurons is that they have a distant axonal projection. Such correlations of cell biological characteristics with specific elements of cortical circuitry will further our understanding of the molecular and cellular properties that are critically linked to a given neuron's role in cortical structure and function.

Animals↗

Deprived somatosensory-motor experience in stumptailed monkey neocortex: dendritic spine density and dendritic branching of layer IIIB pyramidal cells.

Infant macaque monkeys (Macaca arctoides) were individually raised to age 6 months in large clear cubes built into one wall of a control colony that allowed them visual access to it but not tactile contact. The two deprivation conditions (Cond 2 and Cond 3) were equal both in physical size and with respect to partial social isolation. They differed in the degree of somatosensory-motor opportunity available during development in that the Cond 2 chamber was empty, whereas Cond 3 contained ladders, a trapeze, and play objects. Four monkeys from each of these conditions were compared with four colony-reared (Cond CR) monkeys. Neuroanatomical changes were evaluated by using light microscopy in Golgi-Cox-stained neocortex. Dendritic spines on the apical shafts of layer IIIB pyramidal cells were counted in primary motor (MI), somatosensory (SI), and visual (area 17, V1) cortical regions. Layer IIIB pyramidal neurons with somas of medium size were selected from each cortical region and the density of apical dendritic spines determined. The basilar dendritic branches of these same neurons were traced, and the dendritic branching complexity was assessed in order to compare the sensitivity of the dendritic spine and branching measures consequent to deprived rearing. The number of apical dendritic spines was significantly reduced in Cond 2 when compared with either Cond 3 or Cond CR (which did not differ from each other). This occurred in both MI and SI cortex, but not in the visual cortex, the region used as a control for a global brain effect. Branching complexity measured on the same pyramidal neurons was reduced only in MI cortex of Cond 2. These results show spine density, a more direct measure of neuronal connectivity, to be the more sensitive measure of early environmental deprivation. Also, the enriched environment provided by Cond 3 relative to Cond 2 offset the effect of partial social isolation such that both morphometric measures had values comparable to Cond CR monkeys.

Animals↗

Prenatal development of GABA-ergic neurons in the neocortex of the rat.

The present study shows that in the prenatal rat neocortex the GABA immunoreactive neurons are not limited to the marginal, subplate, and intermediate zones, but are also found in all fetal zones of the cerebral anlage. The first GABA-ergic cells are observed on embryonic day 14 in the plexiform primordium. On embryonic day 15, a second population of GABA-ergic cells is observed in the intermediate zone. Beginning on day 16 of gestation and continuing throughout gestation, GABA-ergic neurons are observed in the marginal zone, the subplate zone, the cortical plate, and the ventricular and subventricular zones. Furthermore, while the number of GABA-ergic cells in the cortical plate increases, GABA-ergic neurons in the intermediate zone and subventricular zone decrease in number after embryonic day 19.

Animals↗