Local intra- and interlaminar connections in mouse barrel cortex

Focal injections of horseradish peroxidase (HRP) in dimethylsulfoxide (DMSO) were targeted into mouse somatosensory cortex, in vitro, with a template. Injections were made at different depths and in different locations in the whisker-barrel-defined somatosensory map in order to determine quantitative connectivity patterns within and between barrel-defined cortical columns. Cortices were sectioned in a plane parallel to the pia at 75 microns. Data were collected directly from microscope slides by computer. Data are presented as: 1) Plots of computer-mapped HRP reaction product density in neurons and cell locations for each section in relation to barrel boundaries; 2) histograms of label in cortical layers related to individual barrel-defined columns; 3) polar plots of relative amounts of label within individual barrel columns in sections through each barrel column; 4) vectors which represent HRP reaction product density as a function of direction and distance from the injection site; 5) statistical analysis of the shape of the label distribution pattern in the plane of the cortex as a function of injection site depth; and 6) probability of labeling of any other barrel column given a labeled barrel column. The principal findings are: 1) The pattern of label distribution, after an injection directly above or directly below an individual barrel, is hour-glass shaped with the waist of the hour-glass in layer IV. 2) Connections within barrel cortex are asymmetrical. Barrel-related columns within a row are more strongly interconnected than those in different rows. 3) Connections of the small barrels associated with whiskers on the upper lip are strongest with other small barrels, but strong connections also exist between these small barrels and the larger barrels. 4) The pattern of intracortical connections in SII is not asymmetrical; interlaminar connections in SII are fundamentally different from those in barrel cortex. 5) Quantitative intracortical projection patterns are highly consistent with functional data on intracortical processing of whisker information. As such, the quantitative data clearly indicate the spatial extent and relative magnitude of populations of neurons involved in intracortical processing of sensory information. The spatial arrangements of these intracortical connections, in conjunction with known developmental events, make it highly likely that the distribution of intracortical axons in mouse barrel cortex is sculpted in part by experience.     

Spatial organization of thalamocortical and corticothalamic projection systems in the rat SmI barrel cortex

Axonal tracing techniques were used to examine the distribution of corticothalamic projection neurons in relation to the organization of the thalamocortical recipient zones in the whisker representation of the rat first somatic sensory cortex. Following injection of horseradish peroxidase into the physiologically defined vibrissa area in the ventrobasal complex of the thalamus, labeling in the cortex had a columnar appearance. Dense patches of anterograde labeling were located within the centers of the layer IV barrels and extended superficially through lamina III; the septa between barrels contained considerably less reaction product. Retrogradely labeled neurons were observed in lower layer V and layer VI where they were concentrated preferentially deep to the barrel centers. Regions deep to the septa displayed less overall labeling and a lower relative number of thalamic projecting neurons. Zones having the larger numbers of retrogradely labeled cells also contained terminallike labeling of either corticothalamic or thalamocortical origin. Following an injection that included the posterior group medial to the ventrobasal complex, anterograde labeling in layer IV was located largely in the septa. In conjunction with previous findings concerning the origin and termination of other projection systems in the barrel cortex, these results suggest that a vibrissal column contains a central core zone intimately linked with the ventrobasal thalamus that is bounded by narrower regions of more diverse inputs and outputs that form an interface between adjacent cortical columns.     

Morphology of Golgi-Cox-impregnated barrel neurons in rat SmI cortex

Golgi-Cox-impregnated neurons in the barrel cortex of the rat were studied qualitatively and quantitatively. Adult rat brains were sectioned perpendicular to or parallel to the cortical representation of the large facial vibrissae at 125 micron. Cortical laminar and barrel boundaries were identified from the Nissl counterstain. Over 200 well-impregnated neurons in cortical layers I-IV were selected for classification and further detailed study. Three broad classes of neurons were recognized: (1) pyramidal cells with conical somata, a stout apical dendrite, and spines; (2) class I nonpyramidal cells having small spherical somata and spiny dendrites; and (3) class II nonpyramidal cells having larger ellipsoid somata and smooth or beaded dendrites. The class I cells were further subdivided into "star pyramids" (cells with an apical dendrite) and spiny stellate cells (cells in which all dendrites were of similar length). The class II cells also were subdivided into multiform cells (with multiple dendrites radiating from the soma) and bipolar cells (with two principal dendritic trunks arising from the superficial and deep aspects of the soma). The position of these various cell types in the superficial cortical laminae was mapped in sections normal to the pia. Numerous examples of the class I and class II neurons were drawn with respect to the barrels in layer IV and the extent of their processes noted. Finally, approximately 250 barrel-related class I and II neurons were studied quantitatively using a computer-microscope and digitizing tablet. The density of the Golgi-impregnated neurons corresponds to the pattern of cell density seen with the Nissl counterstain. The various cell types are not uniformly distributed as a function of cortical depth. Cells with apical dendrites were found principally in the supragranular layers and star pyramids in the superficial one-half of layer IV. Spiny stellate cells are concentrated in layer IV and the smooth cells are present in greatest number in deep layer III and deeper layer IV. On the basis of these distributions we suggest that layer IV be subdivided into two sublaminae. The class I and class II neurons can be distinguished according to quantitative criteria which apply in either plane of section used. Class I neurons have smaller projected somal areas, more proximal dendritic branching, and shorter dendrites when class I and II neurons are measured in three dimensions.(ABSTRACT TRUNCATED AT 400 WORDS)     

Crossed corticothalamic and thalamocortical connections of macaque prefrontal cortex

We have conducted a systematic comparison of the ipsilateral (uncrossed) and contralateral (crossed) thalamic connections of prefrontal cortex in macaque monkeys, using cortical implants of horseradish peroxidase pellets and tetramethyl benzidine histochemistry to demonstrate anterograde and retrograde thalamic labeling. Contrary to the prevailing belief that thalamocortical projections are entirely uncrossed, our findings indicate that a modest crossed projection to prefrontal cortex arises from the mesial thalamus, principally the anteromedial and midline nuclei. Also, while confirming that corticothalamic projections are bilateral, we found that the pattern of crossed projections differs from that of uncrossed projections. Projections to mesial thalamic nuclei, specifically to the anteromedial nucleus, the midline nuclei, and the magnocellular part of the mediodorsal nucleus are bilateral, the contralateral projection being nearly as dense as the ipsilateral projection. Projections to the parvicellular part of the mediodorsal and ventral anterior nuclei are also bilateral, but the contralateral projection is much weaker than the ipsilateral projection. Prefrontal projections to the reticular nucleus, medial pulvinar, suprageniculate nucleus, and limitans nucleus appear to be exclusively ipsilateral. These results indicate that prefrontal cortex has prominent bilateral and reciprocal connections with the nuclei of the mesial thalamic region. As this region of the diencephalon has been implicated by anatomical and behavioral studies in memory functions, our findings suggest that prefrontal cortex, through its connections with this region, may be involved in the bilateral integration of mnemonic systems.     

Retrograde tracing of the subset of afferent connections in mouse barrel cortex provided by zincergic neurons

Lateralization of brain functions is a widespread phenomenon in vertebrates. With the well-known lateralization in the processing of human speech and the parallels that exist between birdsong and language, songbirds are interesting for addressing such questions. In the present study, we investigated the central processing of communicative and artificial sounds in starlings, in an integrative part of the song system: the HVC. Neuronal responses to acoustic stimuli were systematically recorded in both hemispheres while the birds were awake, and then anesthetized, allowing quantitative comparisons of the responses obtained in each situation. The total proportion of responsive sites in the HVC of the left and right hemispheres of all birds revealed a significant predominance of the HVC of the right hemisphere when the birds were awake, whereas a high interindividual variability appeared when the birds were anesthetized. When neuronal responses as a whole were further examined, the responses to each type of stimulus appeared to be nonrandomly distributed over the different situations, and some specialization may appear. The results suggest a complex and state-dependent hemispheric specialization toward behaviorally relevant classes of stimuli. In awake birds, the HVC of the left hemisphere may be more involved in the processing of songs that are used in individual recognition at distance, whereas the HVC of the right hemisphere may deal with long and complex sequences of a song that is involved in short-distance communication, especially between males and females. With birds under anesthesia, this pattern is strongly modified.     

Columnar organization of dendrites and axons of single and synaptically coupled excitatory spiny neurons in layer 4 of the rat barrel cortex.

Cortical columns are the functional units of the neocortex that are particularly prominent in the "barrel" field of the somatosensory cortex. Here we describe the morphology of two classes of synaptically coupled excitatory neurons in layer 4 of the barrel cortex, spiny stellate, and star pyramidal cells, respectively. Within a single barrel, their somata tend to be organized in clusters. The dendritic arbors are largely confined to layer 4, except for the distal part of the apical dendrite of star pyramidal neurons that extends into layer 2/3. In contrast, the axon of both types of neurons spans the cortex from layer 1 to layer 6. The most prominent axonal projections are those to layers 4 and 2/3 where they are largely restricted to a single cortical column. In layers 5 and 6, a small fraction of axon collaterals projects also across cortical columns. Consistent with the dense axonal projection to layers 4 and 2/3, the total number and density of boutons per unit axonal length was also highest there. Electron microscopy combined with GABA postimmunogold labeling revealed that most (>90%) of the synaptic contacts were established on dendritic spines and shafts of excitatory neurons in layers 4 and 2/3. The largely columnar organization of dendrites and axons of both cell types, combined with the preferential and dense projections within cortical layers 4 and 2/3, suggests that spiny stellate and star pyramidal neurons of layer 4 serve to amplify thalamic input and relay excitation vertically within a single cortical column.     

Model-based analysis of excitatory lateral connections in the visual cortex

Excitatory lateral connections within the primary visual cortex are thought to link neurons with similar receptive field properties. Here we studied whether this rule can predict the distribution of excitatory connections in relation to cortical location and orientation preference in the cat visual cortex. To this end, we obtained orientation maps of areas 17 or 18 using optical imaging and injected anatomical tracers into these regions. The distribution of labeled axonal boutons originating from large populations of excitatory neurons was then analyzed and compared with that of individual pyramidal or spiny stellate cells. We demonstrate that the connection patterns of populations of nearby neurons can be reasonably predicted by Gaussian and von Mises distributions as a function of cortical location and orientation, respectively. The connections were best described by superposition of two components: a spatially extended, orientation-specific and a local, orientation-invariant component. We then fitted the same model to the connections of single cells. The composite pattern of nine excitatory neurons (obtained from seven different animals) was consistent with the assumptions of the model. However, model fits to single cell axonal connections were often poorer and their estimated spatial and orientation tuning functions were highly variable. We conclude that the intrinsic excitatory network is biased to similar cortical locations and orientations but it is composed of neurons showing significant deviations from the population connectivity rule.     

Postnatal growth of intrinsic connections in mouse barrel cortex.

Surprisingly little is known about the development of connections within a functional area of the cerebral cortex. We examined the postnatal growth of connections in mouse barrel cortex during the second and third weeks after birth, coinciding with the period of rapid synaptogenesis that occurs just after the barrels first form. A barrel is a group of neurons in layer 4 of somatosensory cortex that is part of a cortical column. Each whisker/barrel column is linked anatomically and functionally to a homotopic whisker on the contralateral face. Radial groups of cortical neurons were labeled with the neuronal tracer biotinylated dextran amine in mice ranging in age from postnatal day 8 (P8; P0 is the date of birth) to adulthood. The spatial distributions of retrogradely labeled neurons in different laminae were analyzed. The barrel map in layer 4 was used as a template to compare quantitative data from different animals and to account for substantial changes in barrel and barrel field size during development. Intrinsic projections 1) innervate increasingly more distant targets within barrel cortex up to 3 weeks of age; 2) continue to form in targets after 3 weeks, effectively strengthening existing connections; 3) follow a timetable for growth that is layer-specific; 4) link more distant barrel columns in layer 4 from neurons that are found preferentially in the barrel side and the septa between barrels; and 5) form over the shortest distances between the barrel columns. These data indicate that intrinsic connections in mouse barrel cortex develop by the progressive addition of neuronal connections rather than by sculpting preliminary connections. We describe statistically significant changes in connectivity during development that may be applied to model and assess the development of connections after a variety of experimental perturbations, such as to the environment and/or the genome.     

Innervation of VIP-immunoreactive neurons by the ventroposteromedial thalamic nucleus in the barrel cortex of the rat

We investigated the synaptic terminals of fibers originating in the ventroposteromedial thalamic nucleus (VPM) and projecting to the main input layers (IV/III) of the rat posteromedial barrel subfield. It was our aim to determine whether or not the subpopulation of vasoactive intestinal polypeptide (VIP)-immunoreactive neurons in these layers are directly innervated by the sensory thalamus. Anterograde tracing with Phaseolus vulgaris leucoagglutinin (PHA-L) and immunohistochemistry for VIP were combined for correlated light and electron microscopic examination. Columns of cortical tissue were well defined by barrel-like patches of PHA-L-labeled fibers and boutons in layers IV and III. Within these columns VIP-immunoreactive perikarya were located mainly in supragranular layers. Marked perikarya were also seen in infragranular layers, but their immunoreactivity was often weaker. Granular layer IV, which is the main terminal field for thalamic fibers, contained fewer VIP neurons than supragranular layers. In the light microscope, however, PHA-L-labeled fibers appeared to contact the somata or proximal dendrites of 60–86% of the layer IV VIP neurons. By contrast, only 18–35% of the VIP neurons in the supragranular layers, which receive a moderately dense projection from the VPM, appeared to be contacted. PHA-L-labeled boutons were seen close to 13–25% of infragranular VIP-positive cells. Electron microscopy showed that thalamic fibers formed at most four asymmetric synapses on a single layer IV, VIP-positive neuron. Although the proportion of VIP-positive neurons with labeled synapses was lower in supragranular layers, most of them shared multiple asymmetric synapses with labeled thalamic fibers. Up to six labeled synapses were seen on individual VIP neurons in layer III. We conclude that subpopulations of VIP-immunoreactive neurons, located in layers IV, III, and II are directly innervated by the VPM. These neurons may be involved in the initial stages of cortical processing of sensory information from the large, mystacial vibrissae. Since VIP is known to be colocalized with the inhibitory transmitter GABA, it is likely that VIP neurons participate in the shaping of the receptive fields in the barrel cortex. © 1996 Wiley-Liss, Inc.     

Long-term depression and long-term potentiation in horizontal connections of the barrel cortex

Synaptic plasticity of horizontally orientated connections between barrels, in the barrel cortex of adult mice, was studied in slice preparations cut across rows of barrels. Field potentials were evoked in the middle of one barrel column (in layer IV or V) and recorded in the neighbouring barrel (in layer IV and V). In layer IV, long-term depression (LTD) by 26.5 +/- 5% was first induced by a low-frequency stimulation (2 Hz) applied for 10 min. After 30 min, theta-burst stimulation was delivered to previously depressed connections, resulting in long-term potentiation (LTP) by 28.8 +/- 11.8%. When theta-burst stimulation was delivered without an earlier low-frequency stimulation, no LTP was induced. Similar results were obtained in layer V connections (LTD: 40.6 +/- 12.5%; LTP: 26.9 +/- 12.5%). In layer IV, the application of 100 micro m d,l-2-amino-5-phosphonovaleric acid (APV), an antagonist of NMDA receptors, blocked the induction of both LTD and LTP. These experiments show that a potential for synaptic plasticity is retained in granular and infragranular layers of adult mice.     

Intrinsic excitatory connections in the prefrontal cortex and the pathophysiology of schizophrenia

Working memory, a fundamental cognitive process that is disturbed in schizophrenia, appears to depend upon the sustained activity of specific populations of neurons in the prefrontal cortex. Understanding the neural mechanism(s) that may contribute to the sustained activity of these neurons represents a critical step in predicting the types of alterations in prefrontal circuitry that may be present in schizophrenia, and in determining how such alterations may contribute to the cognitive symptoms of this disorder. This article reviews recent findings which suggest that intrinsic horizontal connections among pyramidal neurons in layer 3 of the dorsolateral prefrontal cortex may provide a critical anatomical substrate for working memory processes, and that alterations in these connections may account for the observations of disturbed working memory, adolescence-related onset of clinical features, and certain pathological changes in the prefrontal cortex of subjects with schizophrenia.     

Thalamocortical and corticothalamic connections of multiple functional domains in posterior parietal cortex of galagos

In prosimian galagos, the posterior parietal cortex (PPC) is subdivided into a number of functional domains where long-train intracortical microstimulation evoked different types of complex movements. Here, we placed anatomical tracers in multiple locations of PPC to reveal the origins and targets of thalamic connections of four PPC domains for different types of hindlimb, forelimb, or face movements. Thalamic connections of all four domains included nuclei of the motor thalamus, ventral anterior and ventral lateral nuclei, as well as parts of the sensory thalamus, the anterior pulvinar, posterior and ventral posterior superior nuclei, consistent with the sensorimotor functions of PPC domains. PPC domains also projected to the thalamic reticular nucleus in a somatotopic pattern. Quantitative differences in the distributions of labeled neurons in thalamic nuclei suggested that connectional patterns of these domains differed from each other.     

Predominance of corticothalamic synaptic inputs to thalamic reticular nucleus neurons in the rat.

Quantitative electron microscopy was used to examine the relative contributions of different types of synapses to the circuitry of the thalamic reticular nucleus (RTN) in the rat. Single RTN cells were injected with Lucifer Yellow (LY) in fixed brain slices and examined after photoconversion; corticothalamic axons and terminals were labeled by anterograde transport of Phaseolus vulgaris-leucoagglutinin (PHA-L); and gamma-aminobutyric acid (GABA)ergic terminals were labeled by postembedding immunocytochemistry. Three types of synapses, made by morphologically distinguishable small terminals (ST), large terminals (LT), and GABAergic terminals, were distributed on all portions of the dendritic trees of injected RTN cells. ST and LT terminals formed asymmetrical, presumed excitatory, synaptic contacts. On proximal dendrites, approximately 50% of the synapses were ST, 30-40% were LT, and 10-25% were GABAergic. On distal dendrites, 60-65% were ST, 20% were LT, and 15% were GABAergic. PHA-L labeling showed that labeled corticothalamic terminals and ST terminals have identical morphological features and the same distribution patterns on RTN dendrites, indicating that the majority of excitatory afferents to RTN neurons are derived from the cerebral cortex. The LT terminals found in smaller numbers are probably derived from collateral axons of thalamocortical relay cells. GABAergic terminals formed by LY-labeled, intra-RTN axon collaterals were relatively few in number, and no dendrodendritic synapses were observed.     

Cytochrome oxidase staining in the rat SmI barrel cortex

Patterns of cytochrome oxidase (CO) activity were examined histochemically in the rat SmI cortex. Discrete regions of high enzymatic activity were centered upon the granule cell aggregates (barrels) in layer IV. Those barrels which correspond to the mystacial vibrissae and make up the posteromedial barrel subfield (PMBSF) were especially interesting in that CO staining revealed distinct metabolic subdivisions which do not have an easily demonstrable cytoarchitectonic counterpart. By analogy with the barrels in mouse PMBSF and with the cytoarchitectonically distinct barrels representing the smaller sinus hairs in the rat we propose that regions of high CO activity denote the "hollow" of the rat PMBSF barrels. In accord with previous physiological studies demonstrating a vertical organization in the rodent barrel cortex, we also noted columns of intense CO activity extending from layer VI through sublamina Vb. The centers of these columns coincided with the centers of the barrels in layer IV. In tangential sections through the infragranular laminae the segmentation of CO-positive zones was less distinct than in layer IV and appeared as bands of heightened activity oriented like the five rows of layer IV barrels. Highly reactive somata and dendrites were observed in both the granular and infragranular CO barrels indicating that some of the increased activity of these regions reflects oxidative metabolism of cortical neurons per se. These patterns of metabolic activity underscore the vertical and horizontal organization of the SmI vibrissa cortex and suggest that neurons located within the central core of a column have functional properties distinct from those located in zones where individual columns interface.     

Morphological heterogeneity of layer VI neurons in mouse barrel cortex

Understanding the basic neuronal building blocks of the neocortex is a necessary first step toward comprehending the composition of cortical circuits. Neocortical layer VI is the most morphologically diverse layer and plays a pivotal role in gating information to the cortex via its feedback connection to the thalamus and other ipsilateral and callosal corticocortical connections. The heterogeneity of function within this layer is presumably linked to its varied morphological composition. However, so far, very few studies have attempted to define cell classes in this layer using unbiased quantitative methodologies. Utilizing the Golgi staining technique along with the Neurolucida software, we recontructed 222 cortical neurons from layer VI of mouse barrel cortex. Morphological analyses were performed by quantifying somatic and dendritic parameters, and, by using principal component and cluster analyses, we quantitatively categorized neurons into six distinct morphological groups. Additional systematic replication on a separate population of neurons yielded similar results, demonstrating the consistency and reliability of our categorization methodology. Subsequent post hoc analyses of dendritic parameters supported our neuronal classification scheme. Characterizing neuronal elements with unbiased quantitative techniques provides a framework for better understanding structure–function relationships within neocortical circuits in general. J. Comp. Neurol. 512:726–746, 2009. © 2008 Wiley‐Liss, Inc.     

Dendritic architecture of corticothalamic neurons in a rat model of microgyria

MATERIALS AND METHODS: Freezing lesions of the sensorimotor cortex resembling focal human microgyria were carried out in newborn rats on first postnatal day (P1). The fine architecture of dendritic trees of corticothalamic neurons was studied in microgyric animals on P90. RESULTS AND DISCUSSION: Compared with controls, layer 5 corticothalamic neurons located in the cortex surrounding the experimental lesion display longer basal dendrites. This finding is discussed with reference to earlier results on dendrites of layer 3 associative neurons, which, in contrast to those of corticothalamic neurons, appear to be markedly simplified.     

Interlaminar and lateral excitatory amino acid connections in the striate cortex of monkey

The intrinsic excitatory amino acid pathways within the striate cortex of monkeys were studied by autoradiographic detection of retrogradely labeled somata following microinjections of D-3H-aspartate (D-3H-Asp) into different layers. The labeled amino acid was selectively accumulated by subpopulations of neurons and, to a small extent, by glial cells, the latter mainly in the supragranular layers. Immunocytochemical detection of neurons containing GABA showed that, apart from a few cells exclusively in layer I, GABAergic neurons do not accumulate D-3H-Asp. Several lines of evidence suggest that D-3H-Asp uptake occurred only at nerve terminals; thus, the pattern of perikaryal labeling allowed the delineation of interlaminar and lateral projections. Neurons in layer I probably project laterally, and layer I receives wide-ranging projections from layer IVB and layer V from cells up to 1300 microns laterally. Some neurons in layer II send a focused projection to lower layer VI. Some neurons in layers II/III project up to 1 mm laterally within their own layer, but relatively few neurons can be labeled in these projections. Similarly, in layers II/III few neurons can be retrogradely labeled from layers V and upper VI, and this projection is organized such that cells closer to the pia project deeper in layer V/VI. The connections of layer IVA could not be revealed separately because of the difficulty of confining injections to this thin sublamina. Neurons in layer IVB project up to 1300 microns within IVB itself. A small number of cells from IVB also project to layers III, IVC-alpha, V, and VI with much more restricted lateral spread. Neurons in upper IVC-alpha send axons to layer IVB with at least 600-800 microns lateral spread. Neurons in lower IVC-alpha/upper IVC-beta project to layer III with at least 300-500 microns lateral spread. The bottom 50-80 microns of layer IVC-beta contains neurons with a very focused projection, apparently exclusively to the layer III/IVA border region. Both layers IVC alpha and beta have rich connections within themselves, the beta sublayer having more restricted lateral connections. Some neurons in layer IVC-beta give a laterally restricted small input to layers IVC-alpha and IVB. Both IVC-alpha and -beta project to layers V and VI, and these projections are spread at least 400 microns laterally. Neurons in layer V project to all layers, but the projection to layers I-III and within layer V itself spread much further laterally than the projections to layers IV and VI.(ABSTRACT TRUNCATED AT 400 WORDS)     

Neonatal sensory deprivation induces selective changes in the quantitative distribution of GABA-immunoreactive neurons in the rat barrel field cortex

Modified activity of the rat vibrissae from birth to adulthood induces profound alterations of the responsiveness and selectivity of neurons in the contralateral somatosensory barrel field cortex of adult rate. Because these functional properties are under the control of the intracortical inhibitory mechanisms, we investigated the effects of unilateral removal of face pad vibrissae on the quantitative distribution of intracortical γ-aminobutyric acid (GABA)-immunoreactive neurons in the rat contralateral and ipsilateral barrel field cortices. This distribution was then compared to a population of control animals. For the entire cortical depth, no significant changes in the density (7,700/mm³ vs. 7,400/mm³), proportion (13.6% vs. 14.4%), or size (11.7 μm vs. 12.5 μm) of GABA-immunoreactive neurons were found in the left contralateral vs. the right ipsilateral barrel field cortex. However, in cortical layer IV, contralateral to the deprivation, the density and proportion of GABA-immunoreactive neurons were lower (6,300/mm³ vs. 13,900/mm³, 6.0% vs. 13.6%; P < 0.01), and these neurons were larger (mean projected height of 15.1 μm vs. 10.8 μm; P < 0.01) than in the ipsilateral barrel field cortex, suggesting a specific loss of GABA expression in a subpopulation of small intracortical neurons. In addition to changes in the contralateral layer IV, GABA-immunoreactive neurons located in the ipsilateral granular layer were also affected. Indeed, their numerical density (13,900/mm³) and proportion (13.6%) were higher (P < 0.01) than in both hemispheres of control animals (average of 10,050/mm³ and 9.4%). On the other hand, GABA-immunoreactive neurons in the ipsilateral layer V were less numerous (5,600/mm³, 15.0%) than in both sides of the controls (average of 10,300/mm³, 22.0%; P < 0.01). Thus, our results show that a unilateral sensory deprivation induces highly selective changes in the intracortical GABA inhibitory circuitry of both hemispheres. These changes are located directly at the input of thalamic afferents and at an output layer of corticofugal and commissural axons and could result in a profound reorganization of the excitatory and inhibitory drives of both sides of the sensory-deprived barrel field cortex. © 1995 Wiley-Liss, Inc.     

DARPP-32, a dopamine and cyclic AMP-regulated phosphoprotein, is present in corticothalamic neurons of the rat cingulate cortex

DARPP-32 immunocytochemistry and retrograde axonal labeling were combined to determine whether DARPP-32-containing neurons of the rat anterior cingulate cortex project to thalamus. Following injections of fluorescent latex microspheres into the mediodorsal thalamic nuclei, a large proportion of the DARPP-32 immunostained neurons in layer VI were also retrogradely labeled. In area 24a, these neurons were mostly found in layer VIb, whereas in area 24b, they were visible throughout layer VI. The presence of DARPP-32 in certain corticothalamic neurons suggests that these cells may be modulated by dopamine, which increases DARPP-32 phosphorylation, and possibly by glutamate, which antagonizes DARPP-32 phosphorylation via the N-methyl-D-aspartate (NMDA) receptor.