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In situ hybridization histochemistry and immunocytochemistry were used to examine lamina- and cell-specific expression of glutamate receptor (GluR) mRNAs and polypeptide subunits in motor and somatosensory cortex of macaque monkeys. Radioactive complementary RNA (cRNA) probes were prepared from cDNAs specific for alpha-amino-3-hydroxy-5-methylisoxozolepropionate (AMPA)/kainate (GluR1-GluR4), kainate (GluR5-GluR7), and N-methyl-D-aspartate (NMDA; NR1, NR2A-NR2D) receptor subunits. AMPA/kainate and NR1, NR2A, and NR2B receptor transcripts show higher expression than other transcripts. All transcripts show lamina-specific patterns of distribution. GluR2 and GluR4 mRNAs show higher expression than do GluR1 and GluR3 mRNAs. GluR6 transcript expression is higher than that of GluR5 and GluR7. NR1 mRNA expression is much higher than that of NR2 mRNAs. NR2C subunit expression is very low except for a very distinct band of high expression in layer IV of area 3b. Immunocytochemistry, using subunit-specific antisera and double labeling for calbindin, parvalbumin, or alpha type II Ca2+/calmodulin-dependent protein kinase (CaMKII-alpha), allowed identification of cell types expressing different subunit genes. GluR1 and GluR5/6/7 immunoreactivity is found in both pyramidal cells and gamma-amino butyric acid (GABA) cells; GluR2/3 immunoreactivity is preferentially found in pyramidal cells, whereas GluR4 immunoreactivity is largely restricted to GABA cells; NMDA receptor subunit immunoreactivity is far greater in excitatory cells than in GABA cells. The density of expression of AMPA/kainate, kainate, and NMDA receptor subunit mRNAs differed within and across the architectonic fields of sensory-motor cortex. This finding and the lamina- and cell-specific patterns of expression suggest assembly of functional receptors from different arrangements of available subunits in specific neuronal populations.

The nomenclature most commonly applied to the motor-related nuclei of the human thalamus differs substantially from that applied to the thalamus of other primates, from which most knowledge of input-output connections is derived. Knowledge of these connections in the human is a prerequisite for stereotactic neurosurgical approaches designed to alleviate movement disorders by the placement of lesions in specific nuclei. Transfer to humans of connectional information derived from experimental studies in nonhuman primates requires agreement about the equivalence of nuclei in the different species, and dialogue between experimentalists and neurosurgeons would be facilitated by the use of a common nomenclature. In this review, the authors compare the different nomenclatures and review the cyto- and chemoarchitecture of the nuclei in the anterolateral aspect of the ventral nuclear mass in humans and monkeys, suggest which nuclei are equivalent, and propose a common terminology. On this basis, it is possible to identify the nuclei of the human motor thalamus that transfer information from the substantia nigra, globus pallidus, cerebellum, and proprioceptive components of the medial lemniscus to prefrontal, premotor, motor, and somatosensory areas of the cerebral cortex. It also becomes possible to suggest the principal functional systems involved in stereotactically guided thalamotomies and the functional basis of the symptoms observed following ischemic lesions in different parts of the human thalamus.

Radioactive complementary RNA probes, made from monkey-specific cDNAs specific for the alpha 1, alpha 2, alpha 4, alpha 5, beta 1, beta 2, and gamma 2 subunits of the gamma-aminobutyric acid A (GABAA) receptor were used for in situ hybridization histochemistry of the primary motor, somatosensory, and anterior parietal areas of the cerebral cortex in macaque monkeys. mRNAs for the alpha 1, beta 2, and gamma 2 subunit polypeptides, which form receptors with the full range of classical properties, are expressed at much higher levels in all areas and show laminar- and sublaminar-specific concentrations. alpha 2, alpha 4, alpha 5, and beta 1 subunit transcripts are expressed at much lower levels but also display individual, laminar-specific concentrations; alpha 5 expression, in particular, is highly expressed in layer IV in the somatosensory and parietal areas and in a layer IV-like band in the motor cortex. In layers in which expression of a particular transcript is high, all neurons may express the gene, but in layers in which expression is moderate, it is possible to detect differences in the degree of labeling of individual neurons for a particular mRNA, and some neurons may not express certain subunit transcripts in detectable amounts. These findings indicate the variability in expression of different GABAA receptor subunits in the cerebral cortex. Laminar differences may indicate the assembly of functional receptors from different arrangements of available subunits in different classes of cells.

In situ hybridization histochemistry and immunocytochemistry, including double immunofluorescence, were used to study the populations of neurons expressing the alpha subunit of type II calcium/calmodulin-dependent protein kinase (CAM II kinase-alpha) or glutamic acid decarboxylase (GAD) in the somatic sensory and motor areas of the macaque monkey cerebral cortex. Sections were subjected to in situ hybridization using radioactive, complementary RNA probes specific for monkey CAM II kinase-alpha or 67 kDa GAD mRNAs. Others were stained immunocytochemically for CAM II kinase-alpha and/or GABA. CAM II kinase-alpha and GAD-67 are expressed in different populations of cells, with no colocalization. CAM II kinase-alpha is expressed in pyramidal cells of layers II-VI, especially layers II and III, as well as in certain small nonpyramidal cells of layer IV in areas 3a, 3b, 1, and 2 and of middle regions of area 4. Both cell types produce excitatory amino acid transmitters. Therefore, as in subcortical regions, CAM II kinase-alpha will be found on the presynaptic side of excitatory synapses but on the postsynaptic side only when these synapses occur on excitatory neurons in the sensory-motor cortex. Quantitative examination showed that CAM II kinase-alpha immunoreactive cells form, on average, approximately 50% of the total neuronal population in each area, while GABA immunoreactive or GAD cRNA hybridized cells form approximately 25-30%. Thus, CAM II kinase-alpha expressing cells cannot account for the total population of non-GABAergic cortical cells, and a certain proportion of the pyramidal cells probably do not express it. In other cortical areas, gene expression for the two molecules is regulated by afferent activity. Therefore, the present results form a necessary basis for studies aimed at determining the role of activity-dependent changes in the balance of excitation and inhibition as a mechanism underlying plasticity of representational maps in the primate sensory-motor cortex.

1. Intracortical microstimulation (ICMS) and horseradish peroxidase (HRP) histochemistry were combined to examine the relationship between intrinsic connections and intracortical microstimulation sites eliciting evoked movements in the forelimb representation of adult macaque monkey motor cortex. 2. The distribution of sites from which stimulation-evoked movements about individual forelimb joints were elicited under anesthesia varied considerably among animals. Identical movements could often be elicited from multiple, noncontiguous sites. 3. After single, small extracellular HRP injections at sites from which thumb movement was evoked, small groups of retrogradely labeled cells and dense patches of axon terminations were found scattered across a wide area of the forelimb representation. Terminal patches were discontinuous and arose from horizontal, intracortical axons. 4. Correlating the HRP labeling with the physiologically defined movement maps revealed a profuse set of intrinsic, bidirectional connections that connect digit representations and representations of movements about the wrist, elbow, and shoulder. 5. HRP injections placed in the forelimb representation close to the physiologically defined face representation resulted in virtually no retrogradely labeled cells or terminal fiber labeling that crossed into the face representation. A patch of anterolaterally placed label that was present may be the dissociated rostrolateral arm area of other authors. 6. Taken together, these data suggest that extensive, horizontally oriented, intrinsic axon collaterals provide inputs to many different forelimb movement representations and may be recruited during complex movements to coordinate the activity of motor cortical zones whose predominant output is to forelimb muscle groups acting synchronously.

Adult monkey sensorimotor cortex consists of several structurally and functionally distinct areas. The developmental sequence through which the characteristic architectonic features and the borders of these areas become resolved was examined in a series of fetal, postnatal and adult monkeys by using Nissl staining, cytochrome oxidase and acetylcholinesterase histochemistry, and immunocytochemistry for GABA and the neuropeptides somatostatin, neuropeptide Y, substance P and cholecystokinin. At the youngest fetal age examined (E110), the pre- and postcentral gyri possess six clearly delineated cellular layers; populations of GABA- and neuropeptide-immunoreactive cells can be identified, but their somatic sensory cortex at E110 lacks areal cytoarchitectonic parcellation. Despite the apparent homogeneity in the cytoarchitecture of the somatic sensory cortex, incipient areal borders are revealed by staining for cytochrome oxidase and acetylcholinesterase activity, and by staining immunocytochemically for several neuropeptides. The motor cortex at E110 differs from that in adults by the presence of a prominent layer IV; a clear cytoarchitectonic border between areas 3a and 4 is detectable at E110, which is also revealed by chemoarchitectonic markers. With increasing age, the characteristic architectonic features gradually emerge and areal cytoarchitectonic borders appear, becoming adult-like by early postnatal ages. The gradual changes in cytoarchitecture are paralleled by redistributions of GABA- and neuropeptide-immunoreactive cells and fiber plexuses. The data demonstrate that the progressive refinement in cytoarchitectonic features and in the distributions of neurotransmitter- and peptide-containing cells occurs primarily during the latter third of gestation. The major changes are temporally coincident with the ingrowth of afferent axonal systems, suggesting that the establishment of connectivity may be capable of modulating finer details of structural or molecular phenotype, particularly intra-areal cytoarchitectonic features and neurotransmitter or peptide expression.

The areal and laminar distribution of GABAA receptor immunoreactivity was examined in fetal, early postnatal and adult monkey sensory-motor cortex by using a monoclonal antibody to the purified GABAA receptor complex (Vitorica et al. 1988). GABAA receptor immunoreactivity was distributed throughout the neuropil, often outlining the unstained somata of pyramidal and non-pyramidal cells. In all areas of the adult sensory-motor cortex, layers I-IIIA exhibited the most intense immunostaining. In deeper layers of the four cytoarchitectonic fields of the first somatic sensory area (SI), layers IIIB and V were lightly stained and alternated with somewhat more intensely stained layers IV and VI. In deeper layers of area 4, the deeper half of layer IIIA through layer VA was lightly immunostained, but layers VB and VI were slightly more intensely immunoreactive. A variable number of nonpyramidal cell somata in the cortex and underlying white matter showed immunoreactive staining. GABAA receptor immunoreactivity was present throughout the sensory-motor cortex from the youngest fetal age examined (E121), but the pattern of immunostaining differed from that in the adult. In all areas, the densest immunoreactivity was found in a diffuse band in layers III and IV and in the subplate zone. Within the subplate zone, the presence of receptor immunoreactivity and some intensely stained neuronal somata at all fetal ages suggests the presence of a synaptic neuropil. With increasing age, gradual changes in the distribution of receptor immunoreactivity occurred, resulting in an adult-like pattern of immunostaining by postnatal day 1.5. These results show that laminar pattern of GABAA receptor distribution closely follows the major concentrations of GABA immunoreactive neurons in adults and it is suggested that laminar changes seen in development are associated with the establishment of afferent connections and inhibitory circuits in the sensory-motor cortex.

The cells of origin of the corticostriatal projection have been identified in squirrel monkeys by the use of the retrograde horseradish peroxidase method. In the subfields of the somatic sensory, motor, parietal and frontal areas of the cortex, cells projecting to the ipsilateral striatum are relatively sparsely distributed and form a group of small- to medium-sized pyramidal cells with an average somal diameter from area to area of 14-16 mum. Such cells are found only in layer V of the cortex (mainly in the more superficial parts of the layer). Since they are consistently smaller than the pyramidal cells of layer V that project to the brainstem and spinal cord and since they lie outside layer VI which gives rise to corticothalamic axons, the corticostriatal axons are unlikely to be collaterals of axons projecting to other sites. The cells of origin of the crossed corticostriatal projection are also found in layer V and are pyramidal cells with somal diameters in the same range as above. They are found only in areas 4, 8, and 6. Studies with the anterograde, autoradiographic method in rhesus, cynomologous and squirrel monkeys, indicate that the somatic sensory areas project to most of the antero-posterior extent of the ipsilateral putamen. Subareas 3a, 3b, 1 and 2 of the somatic sensory cortex project to the same region and the projection overlaps similarly extensive projections from the motor and certain other areas of the cortex. However, in each case the pattern of terminal labeling is in the form of interrupted clusters, strips and bands. A single small injection of the cortex is associated with only one or two such clusters of terminal labeling. This seems to imply that individual corticostriatal fibers end in a very restricted manner and that the terminal ramifications of fibers from one cortical area may alternate in the putamen with those arising in other areas.

The structure of the first somatic sensory area (areas 3, 1 and 2), of the motor area (area 4) and the intervening transitional field (area 3a) is described in the squirrel monkey (Saimiri sciureus) using Nissl, Bodian, Weil and Golgi preparations. The laminar arrangement of both cells and axons is briefly described and this correlated with the distribution of thalamic afferents as identified in experiments conducted with the Nauta and autoradiographic techniques. The latter method was used particularly in order to assess quantitative differences in the density of thalamic projections to the five cytoarchitectonic fields. In the somatic sensory areas thalamic afferents terminate not only in layer IV but a large extent also in a recognizable part of layer III (layer IIIb). In area 4 thalamic terminals fill much of layer III, reaching almost to layer II. In area 3a the extent is intermediate between that seen in areas 3 and 4. It is thought that the extensive spread of thalamic terminals is related to the elongated form of a particular class of spine-bearing cell whose somata are situated in layer IV (Jones, '75). In all areas a small proportion of thalamic afferents end also in layer I. Evidence is presented to indicate that specific afferent fibers emanating from the ventrobasal and ventrolateral complexes of the thalamus terminate in both the deep and superficial parts of layer I while "non-specific" afferents from other thalamic sources end in the superficial part. The autoradiographic studies indicate that there are considerable differences between the number of thalamic afferents ending in area 3 on the one hand and in areas 1 and 2 on the other. Given this and the nature of the degenerating thalamic afferents observed in Nauta preparations, it is possible to identify thalamic afferents in normal Golgi preparations and significant differences are detectable in areas 4, 3 and 1 and 2. It it is as yet uncertain whether the slightly thinner, more sparsely distributed thalamic afferents ending in areas 1 and 2 are branches of those directed primarily to area 3.

Small extracellular injections of HRP were placed into a stratum of corticocortical axons situated immediately deep to area 3b of the monkey somatic sensory cortex. This stratum had previously been demonstrated to contain corticocortical fibers linking the cytoarchitectonic fields of the somatic sensory cortex to one another and certain of them to the motor cortex. This method resulted in extremely successful filling of pyramidal cells, their axons, collateral axon branches, and terminations in areas 3b, 1, and 2 posterior to the injection and in areas 3a and 4 anterior to it. The major finding was that cells with somata situated in any one of these fields and with principal axons traversing the injection site have long collaterals, primarily in layers III and V, which can extend throughout their own cytoarchitectonic field and into one or more other fields. In these fields they give off focused, columnlike concentrations of terminal boutons, which can be separated from one another by 800 micron or more. The anterogradely labeled, primary corticocortical fibers, traced forwards into areas 3a and 4, have virtually identical focal terminations. These findings indicate that interareal connectivity in the sensory-motor cortex can be effected by the axon branches of single cells rather than by separate groups of cells, and this may form a basis for the convergence of place and modality information on single cells in the sensorimotor cortex, a convergence that is not seen in the thalamic input to this cortex.

A double labeling method that permits accurate delineation of the terminals of medial lemniscal fibers was used to determine whether thalamic neurons projecting to motor cortex in the cat are in a position to be contacted by such terminals. Thalamic neurons in the VL nucleus were retrogradely labeled by injections of fluorogold placed in the cytoarchitectonically defined area 4, while lemniscal axons and their terminal boutons were anterogradely labeled, in a Golgi-like manner, from injections of Fast Blue placed under physiological control in different parts of the contralateral dorsal column nuclei. In additional experiments, spinothalamic fibers were similarly labeled by injections of Fast Blue in the spinal cord. The results reveal that there is no significant overlap in the distributions of lemniscal terminals and motor cortex-projecting neurons and that no somata or proximal dendrites of motor cortex-projecting neurons are in a position to receive lemniscal terminals. Spinothalamic terminals, on the other hand, end in clusters around motor cortex-projecting neurons in the VL nucleus as well as in other nuclei and are a more likely route for short latency somatosensory inputs to the motor cortex.

Immunocytochemical methods were used to study the distribution and ultrastructure of serotonin (5-hydroxytryptamine; 5-HT) immunoreactive fibers innervating the monkey sensory-motor cortex. Beaded 5-HT positive fibers were found in all cortical layers of both areas but with relatively fewer in middle cortical layers. Examination of 2 micron-thick plastic sections at the light microscope level, revealed that the vast majority of the bouton-like structures on the fibers lay in the neuropil and not adjacent to neuronal somata. A few beaded immunoreactive fibers were seen around certain pyramidal and non-pyramidal cell somata, very occasionally forming modest pericellular ramifications. Serial reconstructions made from electron micrographs after resectioning the 2 micron-thick sections, revealed that the dilatations of the fibers are 5-HT positive boutons but the boutons examined rarely formed morphologically identifiable synaptic contacts. Of 191 reconstructed boutons only 5 made contacts with obvious membrane specializations, all of which were of the asymmetrical type. No immunoreactive synaptic contacts were seen on pyramidal cell somata in the cortex, nor on dendrites or somata in the white matter underlying the cortex, although 5-HT positive boutons commonly lay closely adjacent to neuronal profiles in both sites. 5-HT fibers in the cortex and white matter have a similar morphological appearance and both myelinated and unmyelinated types are seen.

Large basket cells were identified in Golgi and horseradish peroxidase labeled material from the sensory-motor cortex of adult monkeys. Their morphology was correlated at the light and electron microscopic level with large comparable cells stained immunocytochemically for glutamate decarboxylase. In Golgi-impregnated material these cells have a very large cell body and dendrites that extend through several layers of the cortex with a predominant vertical orientation. The axon is only stained for a few micrometers. The same cells studied electron microscopically in serial sections after gold-toning show very distinctive ultrastructural characteristics: the cell bodies contain a large number of organelles, the nuclei are rounded with homogeneously dispersed chromatin and synapsing onto the somata are many axon terminals, both symmetrical and asymmetrical but the symmetrical type forms 70-80% of the total; dendrites also receive a large number of both symmetrical and asymmetrical synaptic contacts. All the axons of basket cells become myelinated and the Golgi labeling of the initial segments is interrupted at the commencement of the first myelin internode. The axon initial segments receive several symmetrical synaptic contacts in the proximal one-third of their length. The axonal arborization of a basket cell retrogradely labeled in the somatosensory cortex after intracortical injection of horseradish peroxidase was analyzed in detail. The mainly horizontal axonal collaterals of this cell are myelinated for most of their trajectory and have a preferred orientation in the anteroposterior dimension. These axonal collaterals, although very long (more than 1.8 mm), at intervals give rise to a small number of short unmyelinated terminal branches that bear a series of boutons terminaux forming a multi-terminal ending. The multi-terminal endings surround somata and proximal dendrites of pyramidal and non-pyramidal cells. Dense pericellular terminations (baskets or nests) like those drawn by Ramón y Cajal and Marin-Padilla are not formed by the axon of a single basket cell. Thus, basket formations are presumably formed by converging axons from several basket cells. Immunocytochemical material was stained for glutamate decarboxylase, the enzyme involved in the synthesis of gamma-aminobutyrate (GABA). This shows that large glutamate decarboxylase-positive neurons of the same size as those positively identified as basket cells in the Golgi and horseradish peroxidase material have virtually the same morphological characteristics, at both the light and electron microscope levels, as the basket cells.(ABSTRACT TRUNCATED AT 400 WORDS)

Chandelier cell axons were studied in the sensory-motor cortex of adult monkeys. The axonal fields of Golgi-impregnated chandelier cells in layer II in motor cortex are flattened sagittally. The vertical terminal portions of the axons varied both in length and in the numbers converging to form terminations of greater or lesser complexity. Golgi-impregnated plexuses were embedded in plastic and resectioned serially at 2.5-3.0 micrograms. A single axonal field could have as many as 400 terminal rows. All lie 3-13 micrograms beneath pyramidal cell somata. These terminations are not randomly distributed but instead, form clusters. Further resectioning the plastic sections for electron microscopy revealed that all the terminations are on the initial axon segments of pyramidal cells and all form symmetric synaptic contacts. In immunocytochemical material stained for glutamic acid decarboxylase (GAD), the enzyme involved in the synthesis of GABA, GAD-positive boutons were found to form symmetric synaptic contacts with a variety of postsynaptic elements including the axon hillocks and axon initial segments of pyramidal cells. Serial reconstructions from electron micrographs revealed GAD-positive terminals synapsing with the axon initial segment of pyramidal cells joined by cytoplasmic bridges and forming vertically oriented rows identical to those of chandelier cell terminals identified positively in the resectioned Golgi material. The GAD-positive terminals forming initial segment synapses were never continuous with GAD-positive terminals forming axo hillock synapses. The latter probably arise from basket cell axons. Initial segments of pyramidal cell axons in layers II and III were contacted by more GAD-positive terminals than the initial segments of pyramidal cell axons in layer V. The largest pyramidal cells in layer III received the most synapses. Many larger pyramidal cells, identified as callosally projecting cells by the retrograde transport of horseradish peroxidase (HRP), were shown in serial electron micrographs to possess large numbers of initial segment synapses, comparable to those seen in the immunocytochemical material. Serial reconstructions of pyramidal cell axons from axon hillock to the first myelin internode in resectioned Golgi, immunocytochemical and HRP material showed that the number of synapses varied from 2 to 52 for layers II and III and from 2 to 26 for layer V. The number of synapses on the axon hillocks varied from zero to 12. The variability in these terminations may be an important factor in the shaping of the functional properties of the pyramidal cells.

GABAergic neurons have been identified in monkey sensory-motor cerebral cortex by light microscopic, immunocytochemical localization of the GABA synthesizing enzyme, glutamic acid decarboxylase (GAD). All GAD-positive neurons are non-pyramidal cells. Their somata are present in all layers and are evenly distributed across layers II-VI of the motor cortex (area 4), but are found in greater concentrations in layers II, IV and VI of all areas of first somatic sensory cortex (SI; areas 3a, 3b and 1-2). GAD-positive puncta (putative axon terminals) are present throughout the sensory-motor cortex, and they are found immediately adjacent to the somata, dendrites and presumptive axon initial segments of GAD-negative pyramidal cells. In addition, they are observed in close approximation to the somata of both large and small GAD-positive neurons. In area 4, the density of puncta is highest in the superficial cortical layers (layers I-III) and gradually declines throughout the deeper layers. In SI, the highest densities of puncta are present in layer IV, while moderately high densities are found in layers I-III and VI. In areas 3a and 3b, the puncta in layers IV and VI are particularly numerous and form foci that exhibit greater density than adjacent regions. GAD-positive neurons with large somata, 15-33 micron in diameter, are present in layers IIIB-VI of all areas. Such cells have many primary dendrites that radiate in all directions. In addition they have axons that ascend either from the superficial aspect of the somata or from primary dendrites, and that exhibit horizontal collateral branches. These neurons closely resemble the large basket cells (Marin-Padilla, 1969; Jones, 1975), and they may give rise to many of the GAD-positive endings surrounding the somata and proximal dendrites of pyramidal cells in layers III-VI. In addition, small GAD-positive somata are present in all layers, but they are most numerous in layers II and IIIA of all areas and in layer IV of SI. The somata and proximal dendrites of these cells vary from a multipolar shape with small, beaded dendrites, found primarily in layer IV, to bitufted and multipolar shapes with larger, smooth dendrites. The diversity of somal sizes and locations, the variety of dendritic patterns, and the different distributions of GAD-positive puncta, all combine to suggest that several different morphological classes of intrinsic neurons comprise the GABA neurons of monkey cerebral cortex.

Modern anatomical studies show that, contrary to the long-held dogma, there appears to be essentially no convergence of lemniscal, cerebellar, pallidal, or substantial nigral afferents in the thalamus. Each afferent stream defines its own thalamic territory and, through the projection of these thalamic territories to separate cortical territories, the independence of the projections of subcortical motor nuclei upon the cortex is preserved. Only the spinothalamic system appears to gain access to both sensory and motor cortex. A further principle of organization in the sensorimotor thalamus is the presence of individual anatomically and physiologically defined channels, composed of separate afferent inputs and groups of neurons relaying to the cortex. In the somatic sensory relay nuclei the dissociation of cutaneous, deep slowly and rapidly adapting channels is clear-cut in the thalamus and at the input level of the cortex. In the motor system, inputs from each of the deep cerebellar nuclei appear to be dissociated from one another in the thalamus and these in turn from the vestibular and spinothalamic systems. Just as pallidal, nigral and cerebellar pathways are in position to control separate premotor and motor areas of the cortex, so separate channels leading through VLp appear to be in a position to control separate functional units in area 4. Within the cortex itself the absence of corticocortical connections passing from areas 3a and 3b to area 4 appears to indicate that information flow out of these areas is back to areas 1 and 2 for further processing before transmission to area 4 with all the consequences that entails for sensory convergence. Presumably, this route is sufficiently rapid for sensory inputs to reach area 4 at short latency. Although many data are beginning to accrue on the intrinsic structure and connectivity of the sensorimotor cortex, we are still distant from a complete wiring diagram. Circuitry involving thalamic afferents is becoming known slowly and the nature of the cells that are present and their transmitter characteristics are becoming evident from morphological and immunocytochemical studies, along with information on the patterns of axonal ramification of specific cell types, especially of GABAergic cells and of excitatory corticocortical cells.

Neurons in the monkey somatic sensory and motor cortex were labelled immunocytochemically for the GABA synthesizing enzyme, glutamic acid decarboxylase (GAD), and examined with the electron microscope. The somata and dendrites of many large GAD-positive neurons of layers III-VI receive numerous asymmetric synapses from unlabelled terminals and symmetric synapses from GAD-positive terminals. Comparisons with light and electron microscopic studies of Golgi-impregnated neurons suggest that the large labelled neurons are basket cells. Small GAD-positive neurons generally receive few synapses on their somata and dendrites, and probably conform to several morphological types. GAD-positive axons from symmetric synapses on many neuronal elements including the somata, dendrites and initial segments of pyramidal cells, and the somata and dendrites of non-pyramidal cells. Synapses between GAD-positive terminals and GAD-positive cell bodies and dendrites are common in all layers. Many GAD-positive terminals in layers III-VI arise from myelinated axons. Some of the axons form pericellular terminal nests on pyramidal cell somata and are interpreted as originating from basket cells while other GAD-positive myelinated axons synapse with the somata and dendrites of non-pyramidal cells. These findings suggest either that the sites of basket cell terminations are more heterogeneous than previously believed or that there are other classes of GAD-positive neurons with myelinated axons. Unmyelinated GAD-positive axons synapse with the initial segments of pyramidal cell axons or form en passant synapses with dendritic spines and small dendritic shafts and are interpreted as arising from the population of small GAD-positive neurons which appears to include several morphological types.

Callosally projecting cells and the terminal ramifications of their axons were identified in the monkey sensory-motor cortex by retrograde and anterograde labeling techniques, often by double labeling cells and axons in the same animal. Bundles of callosal fibers terminate in small column-like zones 0.5-1 mm wide in the motor cortex (area 4) and in the first (SI) and second (SII) somatic sensory areas. Such columns are aligned in register to form elongated strips extending mediolaterally in the long axes of the pre- and postcentral gyri. Significant portions of area 4, SI and SII, in regions corresponding to the representations of the hand and foot, are not callosally connected. The cells of origin of callosal fibers in SI are largely confined to layer IIIB and form columns and strips corresponding to the above. In connected zones of SI, the callosal connection is reciprocal and precisely point-to point. This and the laminar distribution of the terminal ramifications of callosal fibers (to layers I-IV) suggest that callosal fibers may arise from the terminate upon exactly homotopic, column-like groups of layer IIIB pyramidal cells. Commissurally projecting cells and their terminal ramifications are not limited to particular architectonic fields or particular parts of fields in SI. All architectonic fields of SI project heterotopically to the contralateral SII.