Distributions of Cells and Neurons across the Cortical Sheet in Old World Macaques.

According to previous research, cell and neuron densities vary across neocortex in a similar manner across primate taxa. Here, we provide a more extensive examination of this effect in macaque monkeys. We separated neocortex from the underlying white matter in 4 macaque monkey hemispheres (1 Macaca nemestrina, 2 Macaca radiata, and 1 Macaca mulatta), manually flattened the neocortex, and divided it into smaller tissue pieces for analysis. The number of cells and neurons were determined for each piece across the cortical sheet using flow cytometry. Primary visual cortex had the most densely packed neurons and primary motor cortex had the least densely packed neurons. With respect to differences in brain size between cases, there was little variability in the total cell and neuron numbers within specific areas, and overall trends were similar to what has been previously described in Old World baboons and other primates. The average hemispheric total cell number per hemisphere ranged from 2.9 to 3.7 billion, while the average total neuron number ranged from 1.3 to 1.7 billion neurons. The visual cortex neuron densities were predictably higher, ranging from 18.2 to 34.7 million neurons/cm2 in macaques, in comparison to a range of 9.3-17.7 million neurons/cm2 across cortex as a whole. The results support other evidence that neuron surface densities vary across the cortical sheet in a predictable pattern within and across primate taxa.

Perinatal asphyxia in a nonhuman primate model.

Perinatal asphyxia is a leading cause of brain injury in neonates, occurring in 2-4 per 1,000 live births, and there are limited treatment options. Because of their similarity to humans, nonhuman primates are ideal for performing preclinical tests of safety and efficacy for neurotherapeutic interventions. We previously developed a primate model of acute perinatal asphyxia using 12-15 min of umbilical cord occlusion. Continuing this research, we have increased cord occlusion time from 15 to 18 min and extended neurodevelopmental follow-up to 9 months. The purpose of this report is to evaluate the increase in morbidity associated with 18 min of asphyxia by comparing indices obtained from colony controls, nonasphyxiated controls and asphyxiated animals. Pigtail macaques were delivered by hysterotomy after 0, 15 or 18 min of cord occlusion, then resuscitated. Over the ensuing 9 months, for each biochemical and physiologic parameters, behavioral and developmental evaluations, and structural and spectroscopic MRI were recorded. At birth, all asphyxiated animals required resuscitation with positive pressure ventilation and exhibited biochemical and clinical characteristics diagnostic of hypoxic-ischemic encephalopathy, including metabolic acidosis and attenuated brain activity. Compared with controls, asphyxiated animals developed long-term physical and cognitive deficits. This preliminary report characterizes the acute and chronic consequences of perinatal asphyxia in a nonhuman primate model, and describes diagnostic imaging tools for quantifying correlates of neonatal brain injury as well as neurodevelopmental tests for evaluating early motor and cognitive outcomes.

Cortical connections of the macaque anterior intraparietal (AIP) area.

We traced the cortical connections of the anterior intraparietal (AIP) area, which is known to play a crucial role in visuomotor transformations for grasping. AIP displayed major connections with 1) areas of the inferior parietal lobule convexity, the rostral part of the lateral intraparietal area and the SII region; 2) ventral visual stream areas of the lower bank of the superior temporal sulcus and the middle temporal gyrus; and 3) the premotor area F5 and prefrontal areas 46 and 12. Additional connections were observed with the caudal intraparietal area and the ventral part of the frontal eye field. This study suggests that visuomotor transformations for object-oriented actions, processed in AIP, rely not only on dorsal visual stream information related to the object's physical properties but also on ventral visual stream information related to object identity. The identification of direct anatomical connections with the inferotemporal cortex suggests that AIP also has a unique role in linking the parietofrontal network of areas involved in sensorimotor transformations for grasping with areas involved in object recognition. Thus, AIP could represent a crucial node in a cortical circuit in which hand-related sensory and motor signals gain access to representations of object identity for tactile object recognition.

Do facial gestures, visibility or speed of movement influence gaze following responses in pigtail macaques?

This study investigated whether a human model's facial gestures, speed of head turn and visibility of face influenced gaze-following responses (GFR) in pigtail macaques. A human provided gaze cues by turning her head 90 degrees in one of four directions. Head turns were immediately followed by a facial movement (pucker, eyebrow raise, tongue protrusion, neutral), or were executed swiftly (<0.5 s), slowly (3 s) or whilst facing away from the monkeys. All monkeys reliably followed the gaze in all conditions with no differences between conditions. A greater frequency of GFR was found in females compared to males, and two hypotheses for this finding are discussed.

Cortical Afferents and Myeloarchitecture Distinguish the Medial Intraparietal Area (MIP) from Neighboring Subdivisions of the Macaque Cortex.

The parietal reach region (PRR) in the medial bank of the macaque intraparietal sulcus has been a subject of considerable interest in research aimed at the development of brain-controlled prosthetic arms, but its anatomical organization remains poorly characterized. We examined the anatomical organization of the putative PRR territory based on myeloarchitecture and retrograde tracer injections. We found that the medial bank includes three areas: an extension of the dorsal subdivision of V6A (V6Ad), the medial intraparietal area (MIP), and a subdivision of area PE (PEip). Analysis of corticocortical connections revealed that both V6Ad and MIP receive inputs from visual area V6; the ventral subdivision of V6A (V6Av); medial (PGm, 31), superior (PEc), and inferior (PFG/PF) parietal association areas; and intraparietal areas AIP and VIP. They also receive long-range projections from the superior temporal sulcus (MST, TPO), cingulate area 23, and the dorsocaudal (area F2) and ventral (areas F4/F5) premotor areas. In comparison with V6Ad, MIP receives denser input from somatosensory areas, the primary motor cortex, and the medial motor fields, as well as from visual cortex in the ventral precuneate cortex and frontal regions associated with oculomotor guidance. Unlike MIP, V6Ad receives stronger visual input, from the caudal inferior parietal cortex (PG/Opt) and V6Av, whereas PEip shows marked emphasis on anterior parietal, primary motor, and ventral premotor connections. These anatomical results suggest that MIP and V6A have complementary roles in sensorimotor behavior, with MIP more directly involved in movement planning and execution in comparison with V6A.

Architectonic organization of the inferior parietal convexity of the macaque monkey.

The inferior parietal lobule (IPL) of the macaque monkey constitutes the largest part of Brodmann's area 7. Functional, connectional, and architectonic data have indicated that area 7 is comprised of several distinct sectors located in the lateral bank of the intraparietal sulcus and on the IPL cortical convexity. To date, however, attempts to parcellate the IPL based on architectonic criteria have been controversial, and correlation between anatomical and functional data has been inadequate. In the present study we aimed to determine the number and extent of cytoarchitectonically distinct areas occupying the IPL convexity. To this end, we studied the cytoarchitecture and myeloarchitecture of this region in 28 hemispheres of 17 macaque monkeys. Four distinct areas were identified at different rostrocaudal levels along the IPL convexity and were defined as PF, PFG, PG, and Opt, with area PF corresponding to the rostralmost area and area Opt to the caudalmost one. All areas extend dorsally up to the lateral bank of the intraparietal sulcus, for about 1-2 mm. Areas PF, PFG, and PG border ventrally on opercular areas, whereas area Opt extends ventrally into the dorsal bank of the superior temporal sulcus. Analysis of the distribution of SMI-32 immunoreactivity confirmed the proposed parcellation scheme. Some additional connectional data showed that the four areas project in a differential way to the premotor cortex. The present data challenge the current widely used subdivision of the IPL convexity into two areas, confirming, but also extending the subdivision originally proposed by Pandya and Seltzer.

Development redistribution of photoreceptors across the Macaca nemestrina (pigtail macaque) retina.

Redistributions of monkey cones and rods during the first year after birth include a fivefold increase in peak foveal cone density from 43,000 to 210,000 cones/mm2, a decrease in the diameter of the rod-sparse area, and a two- to threefold decrease in peripheral photoreceptor density. Two weeks before birth, higher cone density is already apparent in the future fovea, as are the nasotemporal asymmetry in cone distribution, a higher density "cone streak" along the horizontal meridian, a large rod-sparse central fovea, and a ring of high rod density. Despite the early appearance of these basic patterns, photoreceptor distribution is not mature until 1 to 5 years postnatally. Total cones varied from 4 million at birth to 3.1 million in the average adult. The two oldest eyes had fewer cones, suggesting up to a 25% loss late in development. There were 60 to 70 million rods in the adult macaque retina and little evidence of postnatal changes in number. Neither of these small changes is sufficient to account for the reduction in peripheral photoreceptor density and both are in the wrong direction to explain increasing foveal density, ruling out a major role for either photoreceptor death or generation. Retinal area increased by a factor of 2.4 from 2 weeks before birth to adulthood. In contrast, the posterior pole of the retina was dimensionally stable throughout this period, with the distance between the fovea and optic disc varying nonsystematically from 3.37 to 4.05 mm. Retinal coverage of the globe was also stable at 48-60%. Thus postnatal growth can be ruled out as a factor in the density changes occurring in central retina. Adult retinas have a higher proportion of both cones and rods in midperiphery, whereas young retinas have a higher proportion of photoreceptors in far periphery. It appears that photoreceptors are radially redistributed from peripheral toward central retina during postnatal development, resulting in the marked increase in foveal cone density and the decrease in the eccentricity of the rod ring. Up to 13 weeks postnatally, midperipheral growth of the retina is substantial and increases with eccentricity. At later ages, expansion continues only in the very far periphery. Retinal growth appears sufficient to explain the decreases in peripheral rod and cone density with age. These and previous data strongly suggest that differentiated photoreceptors, with complex cytology and synaptic contacts, migrate toward the foveal center, explaining the increase in foveal photoreceptor density.(ABSTRACT TRUNCATED AT 400 WORDS)

Thalamic input to mesial and superior area 6 in the macaque monkey.

The aim of the present study was to define the origin of the thalamocortical projections to each of the mesial and superior area 6 areas. To this purpose, restricted injections of neuronal tracers were made into areas F3, F6, F2, and F7 after physiological identification of the injection sites. The results showed that each of these areas receives afferents from a set of thalamic nuclei and that this set differs, qualitatively and quantitatively, according to the injected area. The main inputs to F3 [supplementary motor area properly defined (SMA-proper)] originate in the nuclei ventral lateral, pars oralis (VLo), ventral posterior lateral, pars oralis (VPLo), and ventral lateral, pars caudalis (VLc) as well as in caudal parts of the VPLo and VLc (VPLo/VLc complex). F6 (pre-SMA) is mainly the target of nucleus ventral anterior, pars parvocellularis (VApc), and area X of Olszewski. The input to F2 originates mainly in the VPLo/VLc complex, in VLc, and in VLo. The dorsal part of F7 (supplementary eye field) mainly receives from area X, VApc, and nucleus ventral anterior, pars magnocellularis (VAmc), whereas the ventral F7 is connected with VApc, area X, VLc, and the VPLo/VLc complex. All of the injected areas receive a strong projection from the medial dorsal nucleus (MD). It is concluded that each cortical area is a target of both cerebellar and basal ganglia circuits. F3 and F2 are targets of the so-called "motor" basal ganglia circuit and a cerebellar circuit originating in dorsorostral sectors of dentate and interpositus nuclei. In contrast, F6 and ventral F7 receive a basal ganglia input mainly from the so-called "complex" circuit and a cerebellar input originating in the ventrocaudal sectors of dentate and interpositus nuclei. Finally, with respect to the rest of F7, dorsal F7 also receives a basal ganglia input from the "oculomotor circuit."

Local circuit neurons of macaque monkey striate cortex: IV. Neurons of laminae 1-3A.

We continue our Golgi studies (Lund [1987] J. Comp. Neurol. 257:60-92; Lund et al. [1988] J. Comp. Neurol. 276:1-29; Lund and Yoshioka [1991] J. Comp. Neurol. 331:234-258) of the organization of local circuit, largely gamma-aminobutyric acid (GABA)-containing neurons in macaque monkey visual cortex, area V1, with this account of the local circuit neurons lying in layers 1 and 2/3A. These layers receive intrinsic interlaminar excitatory and inhibitory relays from layers 3B, 4A, 4B, and 5. We describe seven varieties of local circuit neurons with somata within layers 1-2/3A, and we compare the lateral scale of spread of the axons and dendrites of these neurons with the size of the columnar connectional patch domains made by the laterally spreading axon collaterals of pyramidal neurons within the superficial layers (Lund et al. [1993] Cerebral Cortex 3:148-162). We conclude from this comparison that all of the neurons have dendritic fields that are limited to single patch domains. Furthermore, only two of the seven local circuit neuron varieties have sufficient axon spread to influence territory beyond single domains, reaching into neighboring territory likely to differ in function from that occupied by their dendrites. We have identified descending projections from particular varieties to layers 3B, 4A, 4B, and 5 and to the white matter. We discuss the contributions that these interneurons may make to function within the superficial cortical layers, and we summarize our overall conclusions, so far, from our set of studies on interneurons within area V1 of the macaque.

Stratified distribution of synapses in the inner plexiform layer of primate retina.

Distributions of bipolar (B) and amacrine (A) synapses and postsynaptic ganglion cell (G) dendritic profiles in the inner plexiform layer (IPL) were analyzed in EM montages of monkey central and human foveal and peripheral retinae. Synapses and profiles were counted and plotted for each 5% interval of IPL, with 0% at the inner edge of the inner nuclear layer and 100% at the outer edge of the ganglion cell layer. In monkey and human retinae, both A and B synapses occur throughout the IPL, but the ratio of A to B synapses varies from 2:1 to more than 6:1. In the monkey central retina, four bands of A conventional synapses are concentrated at 15, 35, 60, and 80% depth. In the human foveal slope, there are two main A bands at 45 and 85%, whereas in the human periphery, there are five bands at 15, 35, 60, 75, and 90%. In both species, A processes containing large dense-core vesicles are concentrated in three bands at 10-20, 50, and 80-90% depth, corresponding to previously described levels of peptides, dopamine, and GABA. B ribbon synapses are distributed fairly evenly throughout the IPL, with a suggestion of four broadly overlapping bands. Most B ribbons are presynaptic to one A and one G (B----A/G). In the human, there are significantly more B dyads with postsynaptic G's (B----A/G, B----G/G) in the fovea (91%) than in the periphery (66%), implying greater A cell processing peripherally. Also in the human, B terminals containing glycogenlike granules are concentrated in the outer half of the IPL, with agranular terminals in the inner half. Our results demonstrate multiple strata containing different types of synaptic contacts in primate IPL.

Architecture of superior and mesial area 6 and the adjacent cingulate cortex in the macaque monkey.

The agranular frontal cortex is formed by several distinct functional areas. There is no agreement, however, on its cytoarchitectonic organization. The aim of this study was to redefine the cytoarchitectonic organization of superior and mesial area 6 and the adjacent cingulate cortex in the macaque monkey. A particular goal was to find out whether the so-called supplementary motor area (SMA) is cytoarchitectonically different from the rest of area 6 and whether it can be considered as a single, independent cytoarchitectonic area. The results showed that, rostral to F1 (area 4), four architectonic areas can be recognized in the superior (dorsal) and mesial area 6. Two fo them are located on mesial cortical surface (F3 caudally and F6 rostrally) and two on superior cortical convexity (F2 caudally and F7 rostrally). The main cytoarchitectonic features of the five identified areas can be summarized as follows. F1: (1) giant pyramidal cells organized in multiple rows, (2) columnar pattern extending from the white matter to the superficial layers, (3) low cellular density in the lower part of layer III. F3: (1) high cellular density in the lower part of layer III, which fuses with a dense Va, (2) columnar pattern present only in the deepest layer, (3) occasional presence of giant pyramidal cells in layer Vb. F6: (1) prominent layer V, (2) absence of sublayer Vb, (3) homogeneous cell density in superficial layers. F2: (1) thin row of medium-size pyramids in the lowest part of layer III, (2) columnar pattern extending to the superficial layers, (3) dense layer Va, (4) few, scattered giant pyramids in layer Vb. F7: (1) prominent layer V, (2) bipartite layer VI. Areas F1, F2, and F3, as defined cytoarchitectonically, coincided with the homonymous histochemical areas. The present data showed also that area 24 is formed by four subareas: 24a, b, c and d. Areas 24a and b occupy the ventral part of area 24, whereas its dorsal part is formed by area 24c, located rostrally, and area 24d, located caudally. The following features distinguish area 24d from area 24c: (1) larger pyramidal cells in layer V, (2) presence of medium-size pyramidal cells in the lower part of layer III, (3) more prominent columnar pattern, (4) higher myelinization with the presence of an evident horizontal plexus. Mesial area 6 is usually considered as a single functional entity (SMA). Our findings show that this cortical region is formed by two distinct cytoarchitectonic areas.(ABSTRACT TRUNCATED AT 400 WORDS)

Distribution and spatial geometry of dopamine interplexiform cells in the retina. II. External arborizations in the adult rat and monkey.

The morphology and distribution of dopaminergic interplexiform cells in adult rat and monkey retinas were analyzed to determine any correlation with the function of dopamine in the outer retinal layers. The retinas were processed as whole mounts for tyrosine hydroxylase immunohistochemistry. There was a network formed by the sclerally directed processes of interplexiform cells in the inner nuclear, outer plexiform, and outer nuclear layers running throughout the retina. Their density was higher in the superior retina than in the inferior retina of the rat and was especially high in the superior temporal quadrant. The external network in this quadrant was significantly less dense in the monkey than in the rat, as are the interplexiform cells. The somata of interplexiform and other dopaminergic cells were about the same size in both rats and monkeys. Computer-assisted reconstruction of external arborizations of individual cells showed that external processes lay very close to horizontal and photoreceptor cells and also to blood capillaries. Because they were long, thin, and highly varicose; branched at right angles; and often arose from an axon hillock, the external processes were identified as axons. Therefore, we define the dopaminergic interplexiform cells as multiaxonal neurons, with at least one outwardly directed axon that reaches the outer plexiform layer. The function of the network of external processes from the interplexiform dopaminergic cells is discussed in terms of modulating the release of dopamine to external layers.

Organization of thalamic projections to the ventral striatum in the primate.

Although thalamic projections to the dorsal striatum are well described in primates and other species, little is known about thalamic projections to the ventral or "limbic" striatum in the primate. This study explores the organization of the thalamic projections to the ventral striatum in the primate brain by means of wheat germ agglutinin conjugated to horseradish peroxidase (WGA-HRP) and Lucifer yellow (LY) retrograde tracer techniques. In addition, because functional and connective differences have been described for the core and shell components of the nucleus accumbens in the rat and are thought to be similar in the primate, this study also explores whether these regions of the nucleus accumbens can be distinguished by their thalamic input. Tracer injections are placed in different portions of the ventral striatum, including the medial and lateral regions of the ventral striatum; the central region of the ventral striatum, including the dorsal part of the core of the nucleus accumbens; and the shell region of the nucleus accumbens. Retrogradely labeled neurons are located mainly in the midline nuclear group (anterior and posterior paraventricular, paratenial, rhomboid, and reuniens thalamic nuclei) and in the parafascicular thalamic nucleus. Additional labeled cells are found in other portions of the intralaminar nuclear group as well as in other thalamic nuclei in the ventral, anterior, medial, lateral, and posterior thalamic nuclear groups. The distribution of labeled cells varies depending on the area of the ventral striatum injected. All regions of the ventral striatum receive strong projections from the midline thalamic nuclei and from the parafascicular nucleus. In addition, the medial region of the ventral striatum receives numerous projections from the central superior lateral nucleus, the magnocellular subdivision of the ventral anterior nucleus, and parts of the mediodorsal nucleus. After injection into the lateral region of the ventral striatum, few labeled neurons are seen scattered in nuclei of the intralaminar and ventral thalamic groups and occasional labeled cells in the mediodorsal nucleus. The central region of the ventral striatum, including the dorsal part of the core of the nucleus accumbens, receives a limited projection from the midline thalamic, predominantly from the rhomboid nucleus. It receives much smaller projections from the central medial nucleus and the ventral, anterior, and medial thalamic groups. The shell of the nucleus accumbens receives the most limited projection from the thalamus and is innervated almost exclusively by the midline thalamic nuclei and the central medial and parafascicular nuclei. The shell is distinguished from the rest of the ventral striatum in that it receives the fewest projections from the ventral, anterior, medial, and lateral thalamic nuclei.

Representation of face and intra-oral structures in area 3b of macaque monkey somatosensory cortex.

Details of the representation of body regions innervated by the trigeminal nerve were elucidated in monkey cerebral cortex. Microelectrode recording was used to generate somatosensory maps in the posterior bank of the central sulcus and on the exposed cortical surface lateral to the lateral tip of the central sulcus in Macaca nemestrina. The area innervated by the contralateral trigeminal nerve is represented in an 8-mm mediolateral extent of area 3b lateral to the representation of the hand. Lateral to this, still within area 3b, there is an expanded representation of ipsilateral intra-oral structures measuring 6 mm in mediolateral extent. Both representations fill area 3b anteroposteriorly. The ipsilateral representation forms approximately 40% of the trigeminal representation, consistent with the amount of the ventroposterior medial (VPM) thalamic nucleus devoted to representation of ipsilateral intra-oral structures. Comparison of the present results with maps of the face representation in other species of monkey shows a consistent somatotopy of the face between species; size variations are mainly related to the enlarged ipsi- and contralateral representations of the cheek pouches in macaques. The general somatotopy of the trigeminal representation in monkeys is consistent with that in other mammalian species.

Survey of the morphology of macaque retinal ganglion cells that project to the pretectum, superior colliculus, and parvicellular laminae of the lateral geniculate nucleus.

In common with other vertebrates, the primate retina contains a number of different ganglion cell types that project to different regions in the brain. We wanted to determine how the different ganglion cell types, distinguished morphologically, mapped to these regions of the brain. We injected a fluorescent dye into one of three regions of a macaque brain: the superior colliculus (SC), the pretectal region, and the parvicellular laminae of the lateral geniculate nucleus. By means of an in vitro preparation, the retrogradely labelled ganglion cells were intracellularly injected with horseradish peroxidase, so as to reveal their dendritic morphology. When the dendritic-field diameters of the injected cells were plotted against retinal eccentricity, each of the three regions was found to receive input from a distinctive population of cells. The pretectal projection was dominated by cells with large dendritic fields. The SC projection was composed of a number of distinct types, with smaller dendritic fields. Parasol cells project to SC but are extremely rare. In addition to midget ganglion cells, the parvicellular laminae receive inputs from at least two additional groups. Parvicellular bistratified (PB) cells have bistratified dendritic fields, slightly larger than those of parasol cells. Parvicellular giant (PG) cells have dendritic-field diameters larger than that of any parasol cell, ranging from 250 microns to greater than 850 microns--the largest of any primate ganglion cells. In contrast to the retinal projections of the cat, in which a specific ganglion cell type can project to different regions of the brain, each of the regions in this survey appears to receive inputs from its own distinct group of ganglion cells.

Arborisation pattern and postsynaptic targets of physiologically identified thalamocortical afferents in striate cortex of the macaque monkey.

The monosynaptic targets of different functional types of geniculocortical axons were compared in the primary visual cortex of monkeys. Single thalamocortical axons were recorded extracellularly in the white matter by using horseradish-peroxidase-filled pipettes. Their receptive fields were mapped and classified as corresponding to those of parvi- or magnocellular neurons in the lateral geniculate nucleus. The axons were then impaled and injected intraaxonally with horseradish peroxidase. Two magnocellular (MA) and two parvicellular (PA) axons were successfully recovered and reconstructed in three dimensions. The two MA axons arborised mainly in layer 4C alpha, as did the two PA axons in layer 4C beta. Few collaterals formed varicosities in layer 6. Both MA axons had two large, elongated clumps of bouton (approx. 300-500 x 600-1,200 microns each) and a small clump. One PA axon had two clumps (each with a core appr. 200 microns in diameter); the other had only one (appr. 150-200 microns in axon had 1,380; one MA axon had 3,200 boutons; and those of the more extensive MA axon were not counted. The distribution of postsynaptic targets as well as the number of synapses per bouton has been established for a sample of 150 PA boutons and 173 MA boutons from serial ultrathin sections. The MA axons made on average 2.1 synapses per bouton compared to 1.79 for one PA axon and 2.6 for the other. The sample of boutons taken from the two physiological types of axons contacted similar proportions of dendritic spines (52-68%), shafts (33-47%), and somata (0-3%). The postsynaptic elements were further characterized by immunostaining for GABA. All postsynaptic perikarya and some of the dendrites (4.5-9.5% of all targets) were positive for the amino acid. Near the thalamic synapse GABA-negative dendritic shafts frequently contained lamellar bodies, an organelle identical in structure to spine apparatus. Dendritic shafts and spines postsynaptic to the thalamocortical boutons frequently received an adjacent synapse from GABA-immunoreactive boutons. The similarity between the magno-and parvicellular axons in their targeting of postsynaptic elements, including the GABAergic neurons, suggests that the structural basis of the physiological differences between 4C alpha and 4C beta neurons should be sought in other aspects of the circuitry of layer 4C, such as local cortical circuits, or in the far greater horizontal extent of the thalamocortical and GABAergic axons in layer 4C alpha compared to those in the beta subdivision.

Thalamic projections to sensorimotor cortex in the macaque monkey: use of multiple retrograde fluorescent tracers.

We used several fluorescent dyes (Fast Blue, Diamidino Yellow, Rhodamine Latex Microspheres, Evans Blue, and Fluoro-Gold) in each of eight macaques, to examine the patterns of thalamic input to the sensorimotor cortex of macaques 12 months or older. Inputs to different zones of motor, premotor, and postarcuate cortex, supplementary motor area, and areas 3b/1 and 2/5 in the postcentral cortex, were examined. Coincident labeling of thalamocortical neuron populations with different dyes (1) increased the precision with which their soma distributions could be related within thalamic space, and (2) enabled the detection by double labeling, of individual thalamic neurons that were common to the thalamic soma distributions projecting to separate, dye-injected cortical zones. Double-labeled thalamic neurons projecting to sensorimotor cortex were rarely seen in mature macaques, even when the injection sites were only 1-1.5 mm apart, implying that their terminal arborizations were quite restricted horizontally. By contrast, separate neuron populations in each thalamic nucleus with input to sensorimotor cortex projected to more than one cytoarchitecturally distinct cortical area. In ventral posterior lateral (oral) (VPLo), for example, separate populations of cells sent axons to precentral medial, and lateral area 4, medial premotor, and postarcuate cortex, as well as to supplementary motor area. Extensive convergence of thalamic input even to the smallest zones of dye uptake in the cortex (approximately 0.5 mm3) characterized the sensorimotor cortex. The complex forms of these projection territories were explored using 3-dimensional reconstructions from coronal maps. These projection territories, while highly ordered, were not contained by the cytoarchitectonic boundaries of individual thalamic nuclei. Their organization suggests that the integration of the diverse information from spinal cord, cerebellum, and basal ganglia that is needed in the execution of complex sensorimotor tasks begins in the thalamus.

Localization of glycine-containing neurons in the Macaca monkey retina.

Autoradiography following 3H-glycine (Gly) uptake and immunocytochemistry with a Gly-specific antiserum were used to identify neurons in Macaca monkey retina that contain a high level of this neurotransmitter. High-affinity uptake of Gly was shown to be sodium dependent whereas release of both endogenous and accumulated Gly was calcium dependent. Neurons labeling for Gly included 40-46% of the amacrine cells and nearly 40% of the bipolars. Synaptic labeling was seen throughout the inner plexiform layer (IPL) but with a preferential distribution in the inner half. Bands of labeled puncta occurred in S2, S4, and S5. Both light and postembedding electron microscopic (EM) immunocytochemistry identified different types of amacrine and bipolar cell bodies and their synaptic terminals. The most heavily labeled Gly+ cell bodies typically were amacrine cells having a single, thick, basal dendrite extending deep into the IPL and, at the EM level, electron-dense cytoplasm and prominent nuclear infoldings. This cell type may be homologous with the Gly2 cell in human retina (Marc and Liu: J. Comp. Neurol. 232:241-260, '85) and the AII/Gly2 of cat retina (Famiglietti and Kolb: Brain Res. 84:293-300, '75; Pourcho and Goebel: J. Comp. Neurol. 233:473-480, '85a). Gly+ amacrines synapse most frequently onto Gly- amacrines and both Gly- and Gly+ bipolars. Gly+ bipolar cells appeared to be cone bipolars because their labeled dendrites could be traced only to cone pedicles. The pattern of these labeled dendritic trees indicated that both diffuse and midget types of biopolars were Gly+. The EM distribution of labeled synapses showed Gly+ amacrine synapses throughout the IPL, but these composed only 11-23% of the amacrine population. Most of the Gly+ bipolar terminals were in the inner IPL, where 70% of all bipolar terminals were labeled. These findings are consistent with previous data from cats and humans and suggest that both amacrine and bipolar cells contribute to glycine-mediated neurotransmission in the monkey retina.

Anatomical organization of primate visual cortex area VII.

The Golgi Rapid and Kopsch techniques have been used to provide material for an examination of the internal neuronal organization of cortical area VII of the Macaca monkey. The afferent and efferent relationships of area VII, as shown by axoplasmic transport tracing techniques in our own material and in previous studies in other laboratories, are reviewed. Comparison is made between the internal organisation of VI and VII cortex in terms of (1) the marked different in spiny and nonspiny neurons populations of granular layer 4, (2) the difference in relationship of lamina 6 pyramidal neurons to the overlying layers with a shift away from any relationship to granular layer 4 in VII, and (3) differences in the organization of VI lamina 4B and VII lamina 3B--both similarly placed, fiber-rich bands in the two cortical areas. The extrinsic relationships of VI and VII with the lateral geniculate nucleus, superior colliculus, pulvinar, peristriate cortex, cortical area STS, and with each other are compared in terms of laminar locations of efferent neurons and afferent axon terminal fields. It is hoped that this anatomical survey will provide a better foundation for physiological explorations of the region.

Spatial density and distribution of choline acetyltransferase immunoreactive cells in human, macaque, and baboon retinas.

Whole-mounted human, macaque, and baboon retinas were labelled with an antiserum to human choline acetyltransferase (ChAT), by the immunoperoxidase technique. Previous work in nonprimate species has shown that these cells correspond to the starburst amacrine cells. Labelled somata were disposed on either side of the inner plexiform layer, and their processes formed two narrow zones within it. In human retinas, the ratio of labelled somata in the ganglion cell layer (GCL) to those in the inner nuclear layer (nominal Sb/Sa ratio) was about 60/40 at all locations, similar to that found in nonprimate mammalian species. The density of labelled cells in the human GCL ranged from 1,000 to 1,150 mm-2 near the fovea to 300 to 400 mm-2 in the periphery. Labelling tended to be more erratic in macaque retinas. Nevertheless the Sb/Sa ratio was as high as 70/30 and spatial densities were similar to those of humans. The overlap factor in macaque retinas outside the nasal quadrant was about 10 at all retinal eccentricities, based upon dendritic-field sizes from a Golgi study. About each labelled soma there was a region 20 to 120 microns in diameter in which the probability of the occurrence of other labelled somata was lower than elsewhere. No such nonrandomness was found between labeled cells in the GCL and those in the amacrine cell layer. The packing factor was about 0.3 in well-labelled regions, independent of retinal position or spatial density. Published data on ChAT-labelled cells in rabbit and rat show a similar value. This invariance is consistent with the hypothesis that this nonrandomness is a residual consequence of somal contiguity at an early developmental stage.