Showing papers in "The Journal of Comparative Neurology in 1990"

Human photoreceptor topography

Abstract: We have measured the spatial density of cones and rods in eight whole-mounted human retinas, obtained from seven individuals between 27 and 44 years of age, and constructed maps of photoreceptor density and between-individual variability. The average human retina contains 4.6 million cones (4.08-5.29 million). Peak foveal cone density averages 199,000 cones/mm2 and is highly variable between individuals (100,000-324,000 cones/mm2). The point of highest density may be found in an area as large as 0.032 deg2. Cone density falls steeply with increasing eccentricity and is an order of magnitude lower 1 mm away from the foveal center. Superimposed on this gradient is a streak of high cone density along the horizontal meridian. At equivalent eccentricities, cone density is 40-45% higher in nasal compared to temporal retina and slightly higher in midperipheral inferior compared to superior retina. Cone density also increases slightly in far nasal retina. The average human retina contains 92 million rods (77.9-107.3 million). In the fovea, the average horizontal diameter of the rod-free zone is 0.350 mm (1.25 degrees). Foveal rod density increases most rapidly superiorly and least rapidly nasally. The highest rod densities are located along an elliptical ring at the eccentricity of the optic disk and extending into nasal retina with the point of highest density typically in superior retina (5/6 eyes). Rod densities decrease by 15-25% where the ring crosses the horizontal meridian. Rod density declines slowly from the rod ring to the far periphery and is highest in nasal and superior retina. Individual variability in photoreceptor density differs with retinal region and is similar for both cones and rods. Variability is highest near the fovea, reaches a minimum in the midperiphery, and then increases with eccentricity to the ora serrata. The total number of foveal cones is similar for eyes with widely varying peak cone density, consistent with the idea that the variability reflects differences in the lateral migration of photoreceptors during development. Two fellow eyes had cone and rod numbers within 8% and similar but not identical photoreceptor topography.

Distribution of androgen and estrogen receptor mRNA‐containing cells in the rat brain: An in situ hybridization study

Abstract: The distribution of cells that express mRNA encoding the androgen (AR) and estrogen (ER) receptors was examined in adult male and female rats by using in situ hybridization. Specific labeling appeared to be largely, if not entirely, localized to neurons. AR and ER mRNA-containing neurons were widely distributed in the rat brain, with the greatest densities of cells in the hypothalamus, and in regions of the telencephalon that provide strong inputs in the medial preoptic and ventromedial nuclei, each of which is thought to play a key role in mediating the hormonal control of copulatory behavior, as well as in the lateral septal nucleus, the medial and cortical nuclei of the amygdala, the amygdalohippocampal area, and the bed nucleus of the stria terminalis. Heavily labeled ER mRNA-containing cells were found in regions known to be involved in the neural control of gonadotropin release, such as the anteroventral periventricular and the arcuate nuclei, but only a moderate density of labeling for AR mRNA was found over these nuclei. In addition, clearly labeled cells were found in regions with widespread connections throughout the brain, including the lateral hypothalamus, intralaminar thalamic nuclei, and deep layers of the cerebral cortex, suggesting that AR and ER may modulate a wide variety of neural functions. Each part of Ammon's horn contained AR mRNA-containing cells, as did both parts of the subiculum, but ER mRNA appeared to be less abundant in the hippocampal formation. Moreover, AR and ER mRNA-containing cells were also found in olfactory regions of the cortex and in both the main and accessory olfactory bulbs. AR and ER may modulate nonolfactory sensory information as well since labeled cells were found in regions involved in the central relay of somatosensory information, including the mesencephalic nucleus of the trigeminal nerve, the ventral thalamic nuclear group, and the dorsal horn of the spinal cord. Furthermore, heavily labeled AR mRNA-containing cells were found in the vestibular nuclei, the cochlear nuclei, the medial geniculate nucleus, and the nucleus of the lateral lemniscus, which suggests that androgens may alter the central relay of vestibular and auditory information as well. However, of all the regions involved in sensory processing, the heaviest labeling for AR and ER mRNA was found in areas that relay visceral sensory information such as the nucleus of the solitary tract, the area postrema, and the subfornical organ. We did not detect ER mRNA in brainstem somatic motoneurons, but clearly labeled AR mRNA-containing cells were found in motor nuclei associated with the fifth, seventh, tenth, and twelfth cranial nerves. Similarly, spinal motoneurons contained AR but not ER mRNA.(ABSTRACT TRUNCATED AT 400 WORDS)

Topography of ganglion cells in human retina.

Abstract: We quantified the spatial distribution of presumed ganglion cells and displaced amacrine cells in unstained whole mounts of six young normal human retinas whose photoreceptor distributions had previously been characterized. Cells with large somata compared to their nuclei were considered ganglion cells; cells with small somata relative to their nuclei were considered displaced amacrine cells. Within the central area, ganglion cell densities reach 32,000-38,000 cells/mm2 in a horizontally oriented elliptical ring 0.4-2.0 mm from the foveal center. In peripheral retina, densities in nasal retina exceed those at corresponding eccentricities in temporal retina by more than 300%; superior exceeds inferior by 60%. Displaced amacrine cells represented 3% of the total cells in central retina and nearly 80% in the far periphery. A twofold range in the total number of ganglion cells (0.7 to 1.5 million) was largely explained by a similar range in ganglion cell density in different eyes. Cone and ganglion cell number were not correlated, and the overall cone:ganglion cell ratio ranged from 2.9 to 7.5 in different eyes. Peripheral cones and ganglion cells have different topographies, thus suggesting meridianal differences in convergence onto individual ganglion cells. Low convergence of foveal cones onto individual ganglion cells is an important mechanism for preserving high resolution at later stages of neural processing. Our improved estimates for the density of central ganglion cells allowed us to ask whether there are enough ganglion cells for each cone at the foveal center to have a direct line to the brain. Our calculations indicate that 1) there are so many ganglion cells relative to cones that a ratio of only one ganglion cell per foveal cone would require fibers of Henle radiating toward rather than away from the foveal center; and 2) like the macaque, the human retina may have enough ganglion cells to transmit the information afforded by closely spaced foveal cones to both ON- and OFF-channels. Comparison of ganglion cell topography with the visual field representation in V1 reveals similarities consistent with the idea that cortical magnification is proportional to ganglion cell density throughout the visual field.

Unbiased stereological estimation of the number of neurons in the human hippocampus

Abstract: The total numbers of neurons in five subdivisions of human hippocampi were estimated using unbiased stereological principles and systematic sampling techniques. The method addresses the problems associated with the results and conclusions of previous quantitative studies, virtually all of which have been based on biased estimates of neuron densities. For each subdivision, the total number of neurons was calculated as the product of the estimate of the volume of the neuron-containing layers and the estimate of the numerical density of neurons in the layers. Each hippocampus was cut into 3-mm-thick slabs, transverse to the rostrocaudal axis. One 70-micron-thick section from each slab was used in the analysis. The volumes of the layers containing neurons in five major subdivisions of the hippocampus (granule cell layer, hilus, CA3-2, CA1, and subiculum) were estimated with point-counting techniques after delineation of the layers on each section. The numerical densities of neurons in each subdivision were estimated on the same sections with optical disectors. The sampling used in both estimates was performed systematically in all three dimensions. In an example of five hippocampi, the mean numbers of neurons (CV = SD/mean) in the different subdivisions were as follows: granule cells 15 X 10(6) (0.28), hilus 2.0 X 10(6) (0.16), CA3-2 2.7 X 10(6) (0.22), CA1 16 X 10(6) (0.32), subiculum 4.5 X 10(6) (0.19). The stereological measurements contributed approximately 25% of the observed variance. Among the five subjects there was a significant inverse relationship between age (which ranged from 47 to 85 years) and the total number of neurons in CA1 (which ranged from 24 to 11 X 10(6)). An optimized sampling scheme for studies of the number of neurons in the human hippocampus has been designed on the basis of an analysis of variance of the estimates at different levels of the sampling scheme. Counting neurons in the five subdivisions of the human hippocampus with the optimized sampling scheme takes less than 4 hours.

Expression of C-fos-like protein as a marker for neuronal activity following noxious stimulation in the rat

Abstract: C-fos is a proto-oncogene that is expressed within some neurons following depolarization. The protein product, c-fos protein, can be identified by immunohistochemical techniques. Therefore, c-fos expression might be used as a marker for neuronal activity throughout the neuraxis following peripheral stimulation. This study has analyzed patterns of c-fos expression in both control and anesthetized animals and in anesthetized rats subjected to various forms of peripheral stimulation. Labeled cells were counted in the spinal cord, brainstem, hypothalamus, and thalamus. Little c-fos immunoreactivity was found in control animals. Prolonged inhalational anesthesia increased the number of labeled cells at several brainstem sites. Noxious stimulation of anesthetized rats induced c-fos within the neuraxis in patterns consistent with data obtained from electrophysiological studies and in additional locations for which few direct electrophysiological data are available, such as the ventrolateral medulla, the posterior hypothalamic nucleus, and the reuniens and paraventricular thalamic nuclei. Gentle mechanical stimulation was ineffective in inducing c-fos-like protein. The data suggest that c-fos can be used as a transynaptic marker for neuronal activity following noxious stimulation. However, c-fos is expressed only in some kinds of neurons following peripheral stimulation, and it therefore may be an incomplete marker for nociresponsive activity. In addition, at least a few neurons express c-fos protein in the absence of noxious stimulation. Experiments analyzing c-fos expression must be designed with care, as both extraneous stimuli and anesthetic depth influence the results.

Connections of the parabrachial nucleus with the nucleus of the solitary tract and the medullary reticular formation in the rat.

Abstract: We examined the subnuclear organization of projections to the parabrachial nucleus (PB) from the nucleus of the solitary tract (NTS), area postrema, and medullary reticular formation in the rat by using the anterograde and retrograde transport of wheat germ agglutinin-horseradish peroxidase conjugate and anterograde tracing with Phaseolus vulgaris-leucoagglutinin. Different functional regions of the NTS/area postrema complex and medullary reticular formation were found to innervate largely nonoverlapping zones in the PB. The general visceral part of the NTS, including the medial, parvicellular, intermediate, and commissural NTS subnuclei and the core of the area postrema, projects to restricted terminal zones in the inner portion of the external lateral PB, the central and dorsal lateral PB subnuclei, and the "waist" area. The dorsomedial NTS subnucleus and the rim of the area postrema specifically innervate the outer portion of the external lateral PB subnucleus. In addition, the medial NTS innervates the caudal lateral part of the external medial PB subnucleus. The respiratory part of the NTS, comprising the ventrolateral, intermediate, and caudal commissural subnuclei, is reciprocally connected with the Kolliker-Fuse nucleus, and with the far lateral parts of the dorsal and central lateral PB subnuclei. There is also a patchy projection to the caudal lateral part of the external medial PB subnucleus from the ventrolateral NTS. The rostral, gustatory part of the NTS projects mainly to the caudal medial parts of the PB complex, including the "waist" area, as well as more rostrally to parts of the medial, external medial, ventral, and central lateral PB subnuclei. The connections of different portions of the medullary reticular formation with the PB complex reflect the same patterns of organization, but are reciprocal. The periambiguus region is reciprocally connected with the same PB subnuclei as the ventrolateral NTS; the rostral ventrolateral reticular nucleus with the same PB subnuclei as both the ventrolateral (respiratory) and medial (general visceral) NTS; and the parvicellular reticular area, adjacent to the rostral NTS, with parts of the central and ventral lateral and the medial PB subnuclei that also receive rostral (gustatory) NTS input. In addition, the rostral ventrolateral reticular nucleus and the parvicellular reticular formation have more extensive connections with parts of the rostral PB and the subjacent reticular formation that receive little if any NTS input. The PB contains a series of topographically complex terminal domains reflecting the functional organization of its afferent sources in the NTS and medullary reticular formation.

Organization of intrahippocampal projections originating from CA3 pyramidal cells in the rat.

Abstract: The distribution of intrahippocampal projections arising from the CA3 region of the rat hippocampus was investigated using in vitro and in vivo methods. In the in vitro hippocampal slice preparation, single CA3 pyramidal cells were intracellularly labeled with horseradish peroxidase (HRP), and the three-dimensional organization of the axonal plexus was analyzed by using a computer-aided digitizing system. As many as eight primary collaterals originated from the principal axon of CA3 pyramidal cells and these commonly bifurcated further and innervated stratum oriens and stratum radiatum of CA3 and CA1. Within the 400 microns slice, the summed length of all visible collaterals per neuron ranged from 2.6 mm to approximately 12.5 mm. While the CA3 principal axon tended to be relatively smooth, the axonal collaterals bore numerous varicosities that electron microscopy confirmed to be presynaptic boutons. These varicosities occurred, on average, once every 7 microns of collateral length. The distribution of axonal collaterals differed depending on the location of the parent pyramidal cell. Only rarely could CA3 collaterals be followed in the slice to their terminations within CA1. To study the topographic organization of CA3 projections both to other levels of CA3 and to CA1, the anterograde tracer, Phaseolus vulgaris leucoagglutinin (PHA-L) was injected into various transverse and septotemporal levels of CA3. Immunohistochemical visualization of the lectin was conducted in dissected and "extended" hippocampi to facilitate analysis of the topographic distribution of projections along the long or septotemporal axis. Projections from all portions of CA3 reached widespread regions of CA3, CA2, and CA1, but only a few fibers entered the subicular complex and there were no projections to the entorhinal cortex. There were also some CA3 and CA2 projections to the hilus of the dentate gyrus, but these did not enter the granule cell or molecular layers. The CA3 projections to CA1 were organized according to several distinctive and consistent gradients that can generally be summarized as follows. 1. CA3 cells located close to the dentate gyrus (proximal CA3), while projecting both septally and temporally, tended to project more heavily to levels of CA1 located septal to the injection site. CA3 cells located closer to CA1, in contrast, projected more heavily to levels of CA1 located temporally to the injection site. 2. At, or close to, the septotemporal level of the injection, cells located proximally in CA3 gave rise to collaterals that tended to terminate more superficially in stratum radiatum than did those arising from mid and distal levels of CA3.(ABSTRACT TRUNCATED AT 400 WORDS)

Developmental history of the transient subplate zone in the visual and somatosensory cortex of the macaque monkey and human brain

Abstract: The cytological organization and the timetable of emergence and dissolution of the transient subplate zone subjacent to the developing visual and somatosensory cortex were studied in a series of human and monkey fetal brains. Cerebral walls processed with Nissl, Golgi, electron-microscopic, and histochemical methods show that this zone consists of migratory and postmigratory neurons, growth cones, loosely arranged axons, dendrites, synapses, and glial cells. In both species the subplate zone becomes visible at the beginning of the mid-third of gestation as a cell-poor/fiber-rich layer situated between the intermediate zone and the developing cortical plate. The subplate zone appears earlier in the somatosensory than in the visual area and reaches maximal width at the beginning of the last third of gestation in both regions. At the peak of its size the ratio between the width of the subplate zone and cortical plate in the somatosensory cortex is 2:1 in monkey and 4:1 in man while in the occipital lobe these structures have about equal width in both species. The dissolution of the subplate zone begins during the last third of gestation with degeneration of some subplate neurons and the relocation of fiber terminals into the cortex. The subplate zone disappears faster in the visual than in the somatosensory area. The present results together with our previous findings support the hypothesis that the subplate zone may serve as a “waiting” compartment for transient cellular interactions and a substrate for competition, segregation, and growth of afferents originated sequentially from the brain stem, basal forebrain, thalamus, and from the ipsi- and contralateral cerebral hemisphere. After a variable and partially overlapping time period, these fibers enter the cortical plate while the subplate zone disappears leaving only a vestige of cells scattered throughout the subcortical white matter. A comparison between species indicates that the size and duration of the subplate zone increases during mammalian evolution and culminates in human fetuses concomitantly with an enlargement of cortico-cortical fiber systems. The regional difference in the size, pattern, and resolution of the subplate zone correlates also with the pattern of cerebral convolutions. Our findings indicate that, contrary to prevailing notions, the subplate may not be a vestige of the phylogenetically old network but a transient embryonic structure that expanded during evolution to subserve the increasing number of its connections.

Corticocortical connections of anatomically and physiologically defined subdivisions within the inferior parietal lobule.

Abstract: The anatomical and functional organization of the inferior parietal lobule was investigated in macaque monkeys by using anterograde and retrograde anatomical tracing techniques and single cell recording techniques in awake, behaving monkeys. The connections of areas 7a and 7b, and of two previously unexplored areas, the lateral intraparietal area (LIP) and the dorsal prelunate area (DP), were examined in detail. Functional mapping experiments were performed in all four areas. Prior to this study the pathways for visual input to area 7a were unclear. In these experiments we found several direct projections from extrastriate visual areas, including the lateral intraparietal (LIP), dorsal prelunate (DP), parieto-occipital (PO), and medial superior temporal (MST) areas into area 7a. Using the observed laminar patterns of connections between areas 7a, LIP, and DP and other extrastriate cortical areas, we were able to construct a hypothetical flow of visual information processing from striate cortex to area 7a. A broader hierarchy was also produced, which relates the positions of areas 7a, 7b, LIP, and DP to various cortical fields in the parietal, temporal, and frontal lobes. By combining single cell recording techniques in trained monkeys with anatomical tracing techniques, we have parceled the inferior parietal lobule into several subdivisions on the basis of both anatomical and physiological grounds. A clear segregation of visual and somatosensory responses was found in the inferior parietal lobule with areas 7a, LIP, and DP being visual and visual-motor and area 7b being primarily somatosensory. A similar segregation was found anatomically with areas 7a, LIP, and DP being interconnected primarily with other visual cortical areas and area 7b being connected with several somatosensory areas. Area 7b was also found to connect to a few visual cortical areas, and these connections likely account for the small but consistent number of visually responsive cells that are found in this region. Areas LIP, DP, and 7a differed in receptive field and saccade-related properties. Area 7a visual receptive fields were very large and usually bilateral with a small but significant number of them having receptive field centers in the ipsilateral visual field. Area DP and LIP receptive fields were smaller and the receptive field peaks were almost always confined to the contralateral visual field. Areas 7a, DP, and LIP all contained cells with saccade-related responses; however, in area 7a there were fewer saccade cells than area LIP, and presaccadic responses were only observed in area LIP.(ABSTRACT TRUNCATED AT 400 WORDS)

Migration and distribution of two populations of hippocampal granule cell precursors during the perinatal and postnatal periods.

Abstract: Methacrylate-embedded sections and short-survival thymidine radiograms of the hippocampal dentate gyrus were examined in perinatal and postnatal rats in order to trace the site of origin and migration of the precursors of granule cells and study the morphogenesis of the granular layer. The densely packed, spindle-shaped cells of the secondary dentate matrix (a derivative of the primary dentate neuroepithelium) stream in a subpial position towards the granular layer of the internal dentate limb during the perinatal and early postnatal periods. By an accretionary process, the crest of the granular layer forms on day E21 and on the subsequent days the granular layer of the internal dentate limb expands progressively in a lateral direction. Granule cells differentiation, as judged by the transformation of polymorph, darkly staining small cells into rounder, lightly staining larger granule cells, follows the same gradient from the external dentate limb to the internal dentate limb. The secondary dentate matrix is in a process of dissolution by day P5. This matrix is the source of what will later become the outer shell of the granular layer composed of early generated granule cells. The thicker inner shell of the granular layer, formed during the infantile and juvenile periods, derives from an intrinsic, tertiary germinal matrix. On day E22, the dentate migration of the secondary dentate matrix becomes partitioned into two components: (a) the subpial component of extradentate origin, referred to in this context as the first dentate migration, and (b) the second dentate migration. The latter is distributed in the basal polymorph layer throughout the entire dentate gyrus and is henceforth recognized as the tertiary dentate matrix. The tertiary dentate matrix is prominent between days P3 and P10. It is postulated that the great increase in granule cell population during the infantile period is principally due to cells derived from this intrinsic matrix of the dentate gyrus. Between days P20 and P30 the tertiary dentate matrix disappears in the basal polymorph layer and henceforth proliferative cells become largely confined to the subgranular zone at the base of the granular layer. The subgranular zone is the source of granule cells produced during the juvenile and adult periods.

Pathways for motion analysis: Cortical connections of the medial superior temporal and fundus of the superior temporal visual areas in the macaque

Abstract: To identify the cortical connections of the medial superior temporal (MST) and fundus of the superior temporal (FST) visual areas in the extrastriate cortex of the macaque, we injected multiple tracers, both anterograde and retrograde, in each of seven macaques under physiological control. We found that, in addition to connections with each other, both MST and FST have widespread connections with visual and polysensory areas in posterior prestriate, parietal, temporal, and frontal cortex. In prestriate cortex, both areas have connections with area V3A. MST alone has connections with the far peripheral field representations of V1 and V2, the parieto-occipital (PO) visual area, and the dorsal prelunate area (DP), whereas FST alone has connections with area V4 and the dorsal portion of area V3. Within the caudal superior temporal sulcus, both areas have extensive connections with the middle temporal area (MT), MST alone has connections with area PP, and FST alone has connections with area V4t. In the rostral superior temporal sulcus, both areas have extensive connections with the superior temporal polysensory area (STP) in the upper bank of the sulcus and with area IPa in the sulcal floor. FST also has connections with the cortex in the lower bank of the sulcus, involving area TEa. In the parietal cortex, both the central field representation of MST and FST have connections with the ventral intraparietal (VIP) and lateral intraparietal (LIP) areas, whereas MST alone has connections with the inferior parietal gyrus. In the temporal cortex, the central field representation of MST as well as FST has connections with visual area TEO and cytoarchitectonic area TF. In the frontal cortex, both MST and FST have connections with the frontal eye field. On the basis of the laminar pattern of anterograde and retrograde label, it was possible to classify connections as forward, backward, or intermediate and thereby place visual areas into a cortical hierarchy. In general, MST and FST receive forward inputs from prestriate visual areas, have intermediate connections with parietal areas, and project forward to the frontal eye field and areas in the rostral superior temporal sulcus. Because of the strong inputs to MST and FST from area MT, an area known to play a role in the analysis of visual motion, and because MST and FST themselves have high proportions of directionally selective cells, they appear to be important stations in a cortical motion processing system.

Organization of the thalamostriatal projections in the rat, with special emphasis on the ventral striatum.

Abstract: The organization of the thalamic projections to the ventral striatum in the rat was studied by placing injections of the retrograde tracer cholera toxin subunit B in the ventral striatum and small deposits of the anterograde tracer Phaseolus vulgaris-leucoagglutinin (PHA-L) in individual midline and intralaminar thalamic nuclei. In order to provide a complete map of the midline and intralaminar thalamostriatal projections, PHA-L injections were also made in those parts of the intralaminar nuclei that project to the dorsal striatum. The relationship of thalamic afferent fibres with the compartmental organization of the ventral striatum was assessed by combining PHA-L tracing and enkephalin immunohistochemistry. The various midline and intralaminar thalamic nuclei project to longitudinally oriented striatal sectors. The paraventricular thalamic nucleus sends most of its fibres to medial parts of the nucleus accumbens and the olfactory tubercle, whereas smaller contingents of fibres terminate in the lateral part of the nucleus accumbens and the most ventral, medial, and caudal parts of the caudate-putamen complex. The projections of the parataenial nucleus are directed towards central and ventral parts of the nucleus accumbens and intermediate mediolateral parts of the olfactory tubercle. The intermediodorsal nucleus projects to lateral parts of the nucleus accumbens and the olfactory tubercle and to ventral parts of the caudate-putamen. The projection of the rhomboid nucleus is restricted to the rostrolateral extreme of the striatum. A diffuse projection to the ventral striatum arises from neurons ventral and caudal to the nucleus reuniens rather than from cells inside the nucleus. Fibres from the central medial nucleus terminate centrally and dorsolaterally in the rostral part of the nucleus accumbens and medially in the caudate-putamen. Successively more lateral positions in the caudate-putamen are occupied by fibres from the paracentral and central lateral nuclei, respectively. The lateral part of the parafascicular nucleus projects to the most lateral part of the caudate-putamen, whereas projections from the medial part of this nucleus terminate in the medial part of the caudate-putamen and in the dorsolateral part of the nucleus accumbens. Furthermore, a rostral to caudal gradient in a midline or intralaminar nucleus corresponds to a dorsal to ventral and rostral to caudal gradient in the striatum. In the ventral striatum, thalamic afferent fibres in the "shell" region of the nucleus accumbens avoid areas of high cell density and weak enkephalin immunoreactivity.(ABSTRACT TRUNCATED AT 400 WORDS)

Visual receptive field organization and cortico-cortical connections of the lateral intraparietal area (area LIP) in the macaque

Abstract: The visual receptive field physiology and anatomical connections of the lateral intraparietal area (area LIP), a visuomotor area in the lateral bank of the inferior parietal lobule, were investigated in the cynomolgus monkey (Macaca fascicularis). Afferent input and physiological properties of area 5 neurons in the medial bank of the intraparietal sulcus (i.e., area PEa) were also determined. Area LIP is composed of two myeloarchitectonic zones: a ventral zone (LIPv), which is densely myelinated, and a lightly myelinated dorsal zone (LIPd) adjacent to visual area 7a. Previous single-unit recording studies in our laboratory have characterized visuomotor properties of area LIP neurons, including many neurons with powerful saccade-related activity. In the first part of the present study, single-unit recordings were used to map visual receptive fields from neurons in the two myeloarchitectonic zones of LIP. Receptive field size and eccentricity were compared to those in adjacent area 7a. The second part of the study investigated the cortico-cortical connections of area LIP neurons using tritiated amino acid injections and fluorescent retrograde tracers placed directly into different rostrocaudal and dorsoventral parts of area LIP. The approach to area LIP was through somatosensory area 5, which eliminated the possibility of diffusion of tracers into area 7a. Unlike many area 7a receptive fields, which are large and bilateral, area LIP receptive fields were much smaller and exclusively confined to the contralateral visual field. In area LIP, an orderly progression in visual receptive fields was evident as the recording electrode moved tangentially to the cortical surface and through the depths of area LIP. The overall visual receptive field organization, however, yielded only a rough topography with some duplications in receptive field representation within a given rostrocaudal or dorsoventral part of LIP. The central visual field representation was generally located more dorsally and the peripheral visual field more ventrally within the sulcus. The lower visual field was represented more anteriorly and the upper visual field more posteriorly. In LIP, receptive field size increased with eccentricity but with much variability with in the sample. Area LIPv was found to have reciprocal cortico-cortical connections with many extrastriate visual areas, including the parieto-occipital visual area PO; areas V3, V3A, and V4: the middle temporal area (MT); the middle superior temporal area (MST); dorsal prelunate area (DP); and area TEO (the occipital division of the intratemporal cortex). Area LIPv is also connected to area TF in the lateral posterior parahippocampal gyrus.(ABSTRACT TRUNCATED AT 400 WORDS)

GABA : a dominant neurotransmitter in the hypothalamus

Abstract: To study the organization and distribution of the inhibitory amino acid neurotransmitter GABA in the medial hypothalamus, we used a postembedding immunocytochemical approach with colloidal gold. Quantitative analysis showed that half (49%) of all synapsing boutons studied were immunoreactive for GABA, based on immunogold staining of the suprachiasmatic, arcuate, supraoptic, and paraventricular nuclei. This was corroborated with pre-embedding peroxidase immunostaining with antisera against glutamate decarboxylase, the GABA synthetic enzyme. These data suggest that GABA is the numerically dominant neurotransmitter in the hypothalamus, and emphasize the importance of inhibitory circuits in the hypothalamus. Serial ultrathin sections were used to reconstruct GABA immunoreactive boutons and axons in three dimensions. With this type of analysis we found less morphological heterogeneity between GABA immunoreactive boutons than with single ultrathin sections. Single sections sometimes showed boutons containing only small clear vesicles, and other with both clear vesicles and small dense core vesicles. However, with serial sections through individual boutons, dense core vesicles were consistently found at the periphery of the pre-synaptic GABA immunoreactive boutons, suggesting probable co-localization of GABA with unidentified peptides in most if not all boutons throughout the hypothalamus. A positive correlation was found between the density of small clear vesicles and the intensity of immunostaining with colloidal gold particles. GABA immunoreactive axons generally made symmetrical type synaptic specializations, although a small percentage made strongly asymmetrical synaptic specializations. Vesicles in GABA immunoreactive boutons were slightly smaller than those in non-reactive boutons. Synaptic efficacy is related to the position of the synapse on the post-synaptic neuron. While the majority of GABA immunoreactive axons made synaptic contact with dendrites, the distribution of GABA immunoreactive synapses on somata and dendrites was the same as would be expected from a random distribution of all boutons. No preferential innervation of cell bodies by GABA immunoreactive terminals was found. Serial ultrathin sections showed that a GABA immunoreactive axon would sometimes make repeated synaptic contacts with a single postsynaptic neuron, indicating a high degree of direct control by the presynaptic GABAergic cell. Other immunoreactive axons made synaptic contact with a number of adjacent dendrites and cells, suggesting a role for GABA in synchronizing the activity of hypothalamic neurons. Based on the density of immunogold particles per unit area, varying concentrations of immunoreactive GABA were found in different presynaptic boutons in the hypothalamus.

Zebrin II: a polypeptide antigen expressed selectively by Purkinje cells reveals compartments in rat and fish cerebellum.

Abstract: Monoclonal antibody mab-zebrin II was generated against a crude homogenate of cerebellum and electrosensory lateral line lobe from the weakly electric fish Apteronotus leptorhynchus. On Western blots of fish cerebellar proteins, mab-zebrin II recognizes a single polypeptide antigen of apparent molecular weight 36 kD. Immunocytochemistry of apteronotid brains reveals that zebrin II immunoreactivity is confined exclusively to Purkinje cells in the corpus cerebelli, lateral valvula cerebelli, and the eminentia granularis anterior. Other Purkinje cells, in the medial valvula cerebelli and eminentia granularis posterior, are not zebrin II immunoreactive. Immunoreactive Purkinje cells are stained completely, including dendrites, axons, and somata. The antigen seems to be absent only from the nucleus. A similar distribution is seen in catfish, goldfish, and a mormyrid fish. Zebrin II immunoreactivity is also found in the rat cerebellum. Western blotting of rat cerebellar proteins reveals a single immunoreactive polypeptide, with apparent, molecular weight 36 kD, as in the fish. Also as in the fish, staining in the adult rat cerebellum is confined to a subset of Purkinje cells. Peroxidase reaction product is deposited throughout the immunoreactive Purkinje cells with the exception of the nucleus. No other cells in the cerebellum express zebrin II. At higher antibody concentrations, a weak glial cross reactivity is seen in most other brain regions: we believe that this is probably nonspecific. Zebrin II+ Purkinje cells are clustered together to form roughly parasagittal bands interposed by similar non-immunoreactive clusters. In all there are 7 zebrin II+ and 7 zebrin II− compartments in each hemicerebellum. One immunoreactive band is adjacent to the midline; two others are disposed laterally to each side in the vermis; there is a paravermal band; and finally three more bands are identified in each hemisphere. Both in number and position, these compartments correspond precisely to the bands revealed by using another antibody, mabQ113 (anti-zebrin I). In both fish and rat the compartmentation revealed by zebrin II immunocytochemistry is related to the organization of cerebellar afferent and efferent projections and may provide clues as to the fundamental architecture of the vertebrate cerebellum.

Light microscope study of the coexistence of GABA-like and glycine-like immunoreactivities in the spinal cord of the rat.

Abstract: The distributions of GABA-like and glycine-like immunoreactivities in the rat spinal cord were compared by using postembedding immunohistochemistry on semithin sections. In laminae I, II, and III, the proportions of GABA immunoreactive cells were 28%, 31%, and 46%, respectively, whereas for glycine immunoreactive cells the proportions were 9%, 14%, and 30%. Nearly all of the glycine immunoreactive cells in this area were also immunoreactive with the anti-GABA antiserum. In lamina II, some Golgi-stained islet cells were glycine immunoreactive, whereas others were not. Immunoreactive cell bodies were also present in the remainder of the grey matter. Some of these reacted with anti-GABA or antiglycine antiserum; others showed immunoreactivity with both antisera. Immunoreactive axons were found in the ventral and lateral funiculi of the white matter. Many large axons reacted with antiglycine antiserum, whereas GABA-immunoreactive axons were mostly of small diameter. Some large and small axons showed both types of immunoreactivity. These results suggest that the inhibitory neurotransmitters GABA and glycine coexist within cell bodies and axons in the rat spinal cord.

Extrinsic projections from area CA1 of the rat hippocampus: olfactory, cortical, subcortical, and bilateral hippocampal formation projections.

Abstract: Hippocampal area CA1 provides the major cortical output of the hippocampus, but only its projections to the subiculum and lateral septal nucleus are well characterized. The present study reexamines these extrinsic projections by using anterograde and retrograde tracing techniques. Injections of the anterograde tracer Phaseolus vulgaris leucoagglutinin (PHA-L) in the septal one-third of CA1 label axons and terminals in subicular, postsubicular, retrosplenial, perirhinal, and entorhinal cortices, lateral septal nucleus, and diagonal band of Broca. The septal CA1, injections also label terminal fields in contralateral CA1, and in contralateral subicular, postsubicular, perirhinal, and entorhinal cortices. Injections into the splenial one-third of CA1 label axons and terminals in subiculum, postsubiculum, ventral area infraradiata, and lateral septal nucleus, but they do not label axons and terminals on the contralateral side of the brain. Injections in the temporal one-third of CA1 label axons and terminals in subicular, parasubicular, entorhinal, and infraradiata cortices, anterior olfactory nucleus, olfactory bulb, lateral septal nucleus, nucleus accumbens, amygdala, and hypothalamus. The temporal CA1 injections label no axons on the contralateral side of the brain. These data demonstrate that CA1 has more widespread projections than previously appreciated, and they provide the first clear evidence that CA1 projects to the contralateral cortex and to the ipsilateral olfactory bulb, amygdala, and hypothalamus. The results also demonstrate a heterogeneity in the efferent projections originating in different septotemporal levels of CA1.

Cortical projection patterns of the medial septum-diagonal band complex

Abstract: A detailed analysis of the cortical projechns of the medial septum-diagonal band (MS/DR) complex was carried out by means of anterograde transport of Phaseolus vrilgaris leucoagglutinin (PHA-L). The tracer was injected iontophoretically into cell groups of the medial sept,um (MS) and the vertical and horizontal limbs of the diagonal band of Broca (VDR and HDB), and sections were processed immunohistochemically for the intra-axonally transported PHA-L. The labeled efferents showed remarkable differences in regional distribution in the cortical mantle dependent on the position of the injection site in the MSiDB complex, revealing a topographic organization of‘ the MSIDB-cortical projection. In brief, the lateral and intermediate aspects of the HDR, also referred to as the magnoc:cllular preoptic area, predominant.ly project to the olfactory nuclei and the lateral entorhinal cortex. The medial part of the HDR and adjacent caudal (angular) part of the VDB are characterized by widespread, abundant projections to medial mesolimbic, occipital, and lateral entorhinal cortices, olfactory bulb, and dorsal aspects of the subicular and hippocampal areas. Projections from the rostromedial part of the VDB and from the MS are preponderantly aimed at the entire hippocampal and retrohippocampal regions and t,o a lesser degree at the medial mesolirnbic cortex. Furthermore, the MS projections are subject to a clear mediolateral topographic arrangement, such that the lateral MS predominantly projects t,o the ventral/temporal aspects of the subicular complex and hippocampus and to the medial portion ofthe entorhinal cortex, whereas more medially located cells in the MS innervate more septal/dorsal parts of the hippocampal and subicular areas and more lat,eral parts of the entorhinal cortex. PHA-L filled axons have been observed to course through a number of pathways, i.e., the fimbria-fornix system, supracallosal stria, olfactory peduncle, and lateral piriform route (the latter two mainly by the HDB and caudal VDB). Generally, labeled projections were distributed throughout all cortical layers, although clear patterns of lamination were present in several target areas. The richly branching fibers were abundantly provided with both “boutons en passant” and terminal boutons. Both distribution and morphology of the labeled basal forebrain efferents in the prefrontal, cingulate, and occipital cortices closely resemble the distribution and morphology of the cholinergic innervation as revealed by immunohistochemical demonstration of choline acetyltransferase. In contrast, the labeled projections to the olfactory, hippocampal, subicular, and entorhinal areas showed a heterogeneous morphology. Here: the distribution of only the thin varicose projections resembled the distribution of cholinergic fibers.

Connections of the retrosplenial granular a cortex in the rat.

Abstract: Although the retrosplenial granular b cortex (Rgb) is situated in a critical position between the hippocampal formation and the neocortex, surprisingly few studies have examined its connections carefully. The present experiments use both anterograde and retrograde tracing techniques to characterize the connections of Rgb. The main cortical projections from Rgb are to the caudal part of the anterior cingulate cortex, area 18b, retrosplenial granular a cortex (Rga), and postsubiculum, and less dense terminal fields are present in the prelimbic and caudal occipital cortices. The major subcortical projections are to the anterior thalamic nuclei and the rostral pontine nuclei, and very small terminal fields are present in the caudal dorsomedial part of the striatum, the reuniens and reticular nuclei of the thalamus, and the mammillary bodies. Contralaterally, Rgb primarily projects to itself, i.e., homotypically, and more sparsely projects to Rga and postsubiculum. In general, the axons from Rgb terminate ipsilaterally in cortical layers I and III-V and contralaterally in layer V, with a smaller number of terminals in layers I and VI. Thalamic projections from Rgb target the anteroventral and laterodorsal nuclei of the thalamus, with only a few axons terminating in the anterodorsal nucleus, the reticular nucleus, and the nucleus reuniens of the thalamus. Rgb is innervated by the anterior cingulate cortex, precentral agranular cortex, cortical area 18b, dorsal subiculum, and postsubiculum. Subcortical projections to Rgb originate mainly in the claustrum, the horizontal limb of the diagonal band of Broca, and the anterior thalamic nuclei. These data demonstrate that, in the rat, Rgb is a major nodal point for the integration and subsequent distribution of information to and from the hippocampal formation, the midline limbic and visual cortices, and the thalamus. Thus, similarly to the entorhinal cortex, Rgb in the rat is a prominent gateway for information exchange between the hippocampal formation and other limbic areas of the brain.

Occipital cortex in man: organization of callosal connections, related myelo- and cytoarchitecture, and putative boundaries of functional visual areas.

Abstract: Human area 17 is known to contain a single (the primary) visual area, whereas areas 18 and 19 are believed to contain multiple visual areas (defined as individual representations of the contralateral visual hemifield). This is known to be the case in monkeys, where several boundaries between visual areas are characterized by bands of callosal afferents and/or by changes in myeloarchitecture. We here describe the pattern of callosal afferents in (human) areas 17, 18, and 19 as well as their cortical architecture and we infer the position of some visual areas. Sections from occipital lobes of 6 human brains with unilateral occipital infarctions have been silver-impregnated for degenerating axons, thereby revealing callosal afferents to the intact occipital cortex. Their tangential distribution is discontinuous, even in cases with large lesions. A band of callosal afferents straddles the area 17/18 boundary, whereas the remainder of area 17 and a 15-45 mm wide stripe of area 18 adjacent to the callosal band along the 17/18 border are free of them. Patches of callosal afferents alternate with callosal-free regions more laterally in area 18 and in area 19. We conclude that, in man, a second visual area (analogue of V2) lies in area 18, horseshoe-shaped around area 17, and includes the inner part of the acallosal stripe adjacent to the callosal band along the 17/18 boundary. The outer part of this acallosal stripe belongs to a third visual area, which may contain dorsally the analogue of V3 and ventrally that of VP. Thus the lower parts of the second and third visual areas lie on the lingual gyrus, whereas the analogue of the macaque's fourth visual area probably lies on the fusiform gyrus. Although the proposed subdivision of the occipital cortex relies largely on the pattern of callosal afferents, some putative human visual areas appear to have distinct architectonic features. The analogue of V2 is rather heavily myelinated and its layer III contains large pyramidal neurons. Its upper part is not well delimited laterally since adjacent "V" has similar architecture. Its lower part, however, differs clearly from the adjacent "VP," which is lightly myelinated and lacks the large pyramids in layer III. The cortex lateral to "VP" is heavily myelinated and contains fairly large pyramids in layers III and V. The myeloarchitecture of the lateral part of the occipital cortex is not uniform; a very heavily myelinated region stands out in the lateral part of area 19, near the occipito-temporal junction.(ABSTRACT TRUNCATED AT 400 WORDS)

Rod bipolar cells in the mammalian retina show protein kinase C‐like immunoreactivity

Abstract: An antibody directed against protein kinase C (PKC) was applied to various mammalian retinae. In the cat, rat, rabbit, and macaque monkey we found PKC-like immunoreactivity in bipolar cells which had the morphology of rod bipolar cells; in the rat some amacrine cells were also immunoreactive. In the outer plexiform layer, labeled dendrites were always the central elements of the rod spherule invagination, and in the inner plexiform layer only rod bipolar axons and their axon terminals were immunoreactive. The antibody against PKC thus can be used to distinguish rod bipolar cells from cone bipolar cells. The antibody against PKC was used to determine the densities of rods and rod bipolar cells in the cat retina. In the central retina we found a rod to rod bipolar ratio of 16 to 1, in the periphery the ratio increases to 25 to 1. In freshly dissociated retina, cells with rod bipolar morphology could be identified; these cells were also labeled with the anti-PKC antibody. Hence, PKC-like immunoreactivity can be used to recognize rod bipolar cells in vitro.

Two transpallidal pathways originating in the rat nucleus accumbens.

Abstract: The striatopallidal projection originating in the nucleus accumbens was investigated by using anterograde transport of PHA-L in combination with peptide immunohistochemistry in order to localize the injection sites and transported lectin with respect to neurochemically defined subterritories in the nucleus accumbens and subcommissural ventral pallidum. The results reported here supplement our previous observations, which indicated that the subcommissural ventral pallidum of the rat comprises two immunohistochemically defined subterritories (Zahm and Heimer, '88: J. Comp. Neurol., 272:516-535) which give rise to dichotomous downstream projection systems (Zahm, '89: Neuroscience, 30:33-50). The present data indicate that the neurotensin immunoreactivity-rich ventromedial district of ventral pallidum receives its accumbal input almost exclusively from the shell district of the nucleus accumbens. The accumbal core, alternatively, projects to the dorsolateral ventral pallidal subterritory that lacks appreciable neurotensin immunoreactivity and in many other respects more resembles the adjoining striatopallidal components of the caudate-putamen. In addition to direct topographic relationships in the frontal plane among the accumbal injection sites and ventral pallidal terminations, it was observed that more caudally placed core injections resulted in patches of striatopallidal terminations that were more caudally located in ventral pallidum. Shell injections, in contrast, produced columns of terminations that extended continuously from the rostralmost level that they appeared to the caudal end of ventromedial ventral pallidum. The accumbal shell, its exclusive projection to the ventromedial subterritory in the subcommissural ventral pallidum, and the previously reported, almost exclusive projection of that pallidal subdistrict to the mesencephalic ventral tegmental area are discussed in terms of a number of other neurochemical and hodological features that serve to distinguish them sufficiently to suggest that they represent a uniquely specialized part of the basal ganglia.

Mosaic organization of the hippocampal neuroepithelium and the multiple germinal sources of dentate granule cells

Abstract: This study deals with the site of origin, migration, and settling of the principal cell constituents of the rat hippocampus during the embryonic period, The results indicate that the hippocampal neuroepithelium consists of three morphogenetically discrete components—the Ammonic neuroepithelium, the primary dentate neuroepithelium, and the fimbrial glioepithelium—and that these are discrete sources of the large neurons of Ammon's horn, the smaller granular neurons of the dentate gyrus, and the glial cells of the fimbria The putative Ammonic neuroepithelium is marked in short-survival thymidine radiograms by a high level of proliferative activity and evidence of interkinetic nuclear migration from day E16 until day E19 On days E16 and E17 a diffuse band of unlabeled cells forms outside the Ammonic neuroepithelium These postmitotic cells are considered to be stratum radiatum and stratum oriens neurons, which are produced in large numbers as early as day E15 A cell-dense layer, the incipient stratum pyramidale, begins to form on day E18 and spindle-shaped cells can be traced to it from the Ammonic neuroepithelium This migratory band increases in size for several days, then declines, and finally disappears by day E22 It is inferred that this migration contains the pyramidal cells of Ammon's horn that are produced mostly on days E17 through E20 The putative primary dentate neuroepithelium is distinguished from the Ammonic neuroepithelium during the early phases of embryonic development by its location, shape, and cellular dynamics It is located around a ventricular indentation, the dentate notch, contains fewer mitotic cells near the lumen of the ventricle than the Ammonic neuroepithelium, and shows a different labeling pattern both in short-survival and sequential-survival thymidine radiograms By day E18, the reduced primary dentate neuroepithelium is surrounded by an aggregate of proliferative cells; this is the secondary dentate matrix On the subsequent days spindle-shaped cells that have retained their proliferative capacity migrate from the progressively receding secondary dentate matrix to the dentate gyrus itself The latter, representing a tertiary germinal matrix, becomes highly active during the perinatal period The putative fimbrial glioepithelium is situated between the primary dentate neuroepithelium and the tip of the hippocampal rudiment Observations in methacrylate sections and thymidine radiograms suggest that the cells of this germinal matrix, unlike typical neuroepithelial cells, do not undergo interkinetic nuclear migration The fimbrial glioepithelium is clearly present by day E16, two days before the fimbria becomes a distinct fiber tract As the fimbria emerges, cells of the putative glial matrix migrate into it

Afferent and efferent innervation of the cat cochlea: quantitative analysis with light and electron microscopy.

Abstract: The purpose of the present study was to describe the longitudinal and radial gradients of cochlear innervation in the cat. To this end, afferent and efferent terminals of both the inner (IHC) and outer hair cell (OHC) regions were reconstructed from serial ultrathin sections at six and eight cochlear locations, respectively, corresponding to roughly octave intervals of characteristic frequency (CF). Analysis of the afferent innervation of the IHCs showed (1) the number of radial fibers per IHC rises from 10 per IHC at the 0.25 kHz region to a maximum of 30 per IHC at the 10 kHz locus; (2) branching of radial fibers is essentially restricted to regions apical to the 1.0 kHz point; and (3) there are significant differences in synaptic-body morphology for synapses on different sides of the IHC, corresponding to known differences in afferent threshold and rate of spontaneous activity. With respect to efferent innervation in the IHC area, we found (1) that there were numerous vesicle-filled terminals contacting every IHC examined; however, those with obvious synaptic specialization were confined to the most apical regions; and (2) there were roughly the same numbers of efferent synapses per radial fiber at all cochlear locations; however, at each location, radial fibers contacting the modiolar side of the hair cell (corresponding to high-threshold afferents) showed significantly more efferent synapses than radial fibers contacting the pillar side. Analysis of the OHC afferent innervation showed (1) a clear rise in numbers of terminals per OHC from roughly 3 per cell in the base to 15 per cell in the apex, (2) no systematic differences in the numbers of terminals as a function of OHC row, and (3) that synaptic bodies at the OHC afferent synapse are common only apical to the 1.0 kHz locus. Counts of efferent terminals on OHCs revealed (1) maximal numbers (9 per OHC) between the 6 and 24 kHz regions and (2) striking decrease in terminal counts from first- to third-row OHCs. Ultrastructural data on efferent innervation were compared quantitatively with light-microscopic analysis of cochleas immunostained (with antibody to synaptophysin) to reveal all vesiculated terminals.

Supplementary eye field as defined by intracortical microstimulation: connections in macaques.

Abstract: In macaques, the frontal eye field and the recently defined supplementary eye field play a role in the production of eye movements. Whereas the structure and function of the frontal eye field are well understood, little is known about the supplementary eye field. The goal of this study was to determine the connections of the physiologically defined supplementary eye field. In each case, the location of the supplementary eye field was determined by using intracortical microstimulation, the borders were marked with small electrolytic lesions, and horseradish peroxidase conjugated to wheat germ agglutinin was injected into the supplementary eye field. After the tissue was incubated with tetramethyl benzidine, it was determined that in three cases the injection site was confined to the physiologically defined supplementary eye field. The present results indicate that the supplementary eye field is reciprocally connected with the claustrum, ventral anterior nucleus, including pars magnocellularis, nucleus X, posterior subdivision of the ventral lateral nucleus, multiform, parvocellular, magnocellular, and densocellular subdivisions of the medial dorsal nucleus, central lateral nucleus, parafascicular nucleus, and suprageniculate-limitans complex. The supplementary eye field projects to the putamen, caudate, reticular nucleus of the thalamus, central densocellular nucleus, zona incerta, subthalamic nucleus, rostral interstitial nucleus of the medial longitudinal fasciculus, parvocellular part of the red nucleus, intermediate and deep layers of the superior colliculus, central gray, cuneiform nucleus, mesencephalic reticular formation, pontine gray, nucleus reticularis tegmenti pontis, and nucleus reticularis pontis oralis. The supplementary eye field is reciprocally and bilaterally connected with periprincipal and inferior prefrontal cortex, with periarcuate cortex, including the frontal eye field, the frontal ventral region, and with postarcuate premotor cortex, and cortex surrounding the supplementary eye field, including the supplementary motor area. The supplementary eye field is also reciprocally connected ipsilaterally with cortex in and around the cingulate sulcus and the intraparietal sulcus, whereas cortex within the superior temporal sulcus projects to the supplementary eye field. The connections of the physiologically defined supplementary eye field are compared to previously demonstrated connections of the supplementary motor region and of the physiologically defined frontal eye field. Comparisons between the connections of the frontal and supplementary eye fields reveal that both regions are connected with structures related to visuomotor functions, but the frontal eye field has more extensive connections with vision-related structures, and the supplementary eye field has more extensive connections with structures related to prefrontal and skeletomotor functions. Such connectional differences suggest functional differences between these two sensorimotor regions of the frontal lobe.

Cytological and quantitative characteristics of four cerebral commissures in the rhesus monkey.

Abstract: The number, types, and distribution of distinct classes of axons and glia in four cerebral commissures of the adult rhesus monkey (Macaca mulatta) were determined using electron microscopic and immunocytochemical methods. The two neocortical commissures, the corpus callosum, and the anterior commissure contain small but cytologically distinct archicortical components: the hippocampal commissure, which lies ventral to the splenium of the corpus callosum, and the basal telencephalic commissure, which forms a small crescent at the anterior margin of the anterior commissure. Each archicortical pathway is delineated from the adjacent neocortical commissure by a glial capsule. The glia cells that form this border are immunoreactive with antisera directed against glial fibrillary acidic protein (GFAP) and issue long processes that form numerous desmosomal junctions with one another. Braids of these glial processes envelop axonal fascicles within the archicortical commissures. In contrast, the GFAP-positive cells of the corpus callosum and anterior commissure are randomly distributed cells with relatively short stellate processes that do not form boundaries around axon fascicles. Quantitative electron microscopic analysis reveals that approximately 60 million axons connect the two cerebral hemispheres: the corpus callosum contains 56.0 million +/- 3.8 million axons (n = 8), the anterior commissure contains 3.15 million +/- 0.24 million axons (n = 8), the hippocampal commissure has 237,000 axons +/- 31,000 (n = 6), and the basal telencephalic commissure has 193,000 axons +/- 28,000 (n = 5). The number of axons is not directly proportional to the cross-sectional area in any of the commissures because of variation in axonal composition. On the basis of an estimate of approximately 3 billion neurons in the monkey cortex (Shariff, '53), we estimate that between 2 and 3% of all cortical neurons project to the opposite cerebral hemisphere. Subregions of the corpus callosum as well as each of the other commissures consist of characteristic subsets of five classes of axons and contain different proportions of myelinated to unmyelinated fibers. The largest myelinated axons and the smallest proportion of unmyelinated axons (approximately 6%) are found in regions of the corpus callosum that carry projections from primary sensory cortices, whereas the smallest myelinated axons and largest proportion of unmyelinated axons (approximately 30%) are found in regions of the corpus callosum that carry projections from association cortices. Axon composition in the anterior commissure is uniform and resembles that of callosal sectors that contain association projections.(ABSTRACT TRUNCATED AT 400 WORDS)

Organization of cortical, basal forebrain, and hypothalamic afferents to the parabrachial nucleus in the rat

Abstract: In a previous study (Herbert et al., J. Comp. Neurol. [1990];293:540-580), we demonstrated that the ascending afferent projections from the medulla to the parabrachial nucleus (PB) mark out functionally specific terminal domains within the PB. In this study, we examine the organization of the forebrain afferents to the PB. The PB was found to receive afferents from the infralimbic, the lateral prefrontal, and the insular cortical areas; the dorsomedial, the ventromedial, the median preoptic, and the paraventricular hypothalamic nuclei; the dorsal, the retrochiasmatic, and the lateral hypothalamic areas; the central nucleus of the amygdala; the substantia innominata; and the bed nucleus of the stria terminalis. In general, forebrain areas tend to innervate the same PB subnuclei from which they receive their input. Three major patterns of afferent termination were noted in the PB; these corresponded to the three primary sources of forebrain input to the PB: the cerebral cortex, the hypothalamus, and the basal forebrain. Hypothalamic afferents innervate predominantly rostral portions of the PB, particularly the central lateral and dorsal lateral subnuclei. The basal forebrain projection to the PB ends densely in the external lateral and waist subnuclei. Cortical afferents terminate most heavily in the caudal half of the PB, particularly in the ventral lateral and medial subnuclei. In addition, considerable topography organization was found within the individual projections. For example, tuberal lateral hypothalamic neurons project heavily to the central lateral subnucleus and lightly to the waist area; in contrast, caudal lateral hypothalamic neurons send a moderately heavy projection to both the central lateral and waist subnuclei. Our results show that the forebrain afferents of the PB are topographically organized. These topographical differences may provide a substrate for the diversity of visceral functions associated with the PB.

Burst generating and regular spiking layer 5 pyramidal neurons of rat neocortex have different morphological features

Abstract: Intracellular recordings were obtained from pyramidal neurons in layer 5 of rat somatosensory and visual cortical slices maintained in vitro. When directly depolarized, one subclass of pyramidal neurons had the capacity to generate intrinsic burst discharges and another generated regular trains of single spikes. Burst responses were triggered in an all-or-none manner from depolarizing afterpotentials in most bursting neurons. Regular spiking cells responded to electrical stimulation of ascending afferents with a typical EPSP-IPSP sequence, whereas IPSPs were hard to detect in bursting cells. Orthodromic activation of the latter evoked a prominent voltage-dependent depolarization that could trigger a burst response. Intracellularly labelled bursting and regular spiking cells were located in layer 5b, but had distinctly different morphologies. Bursting neurons had a large pyramidal soma, a gradually emerging apical dendrite, and an extensive apical and basal dendritic tree. Their axonal collateral arborization was predominantly limited to layers 5/6. In contrast, regular spiking cells had a more rounded soma with abruptly emerging apical dendrite, a smaller dendritic arborization, and 2 to 8 ascending axonal collaterals that arborized widely in the supragranular layers. Both bursting and regular spiking cells had main axons that entered the subcortical white matter. These data show that some subgroups of pyramidal neurons within the deeper parts of layer 5 of rat cortex are morphologically and physiologically distinct and have different intracortical connections. Bursting cells presumably function to amplify and synchronize cortical outputs, whereas regular spiking output neurons provide excitatory feedback to neurons at all cortical levels and receive a more effective orthodromic inhibitory input. These data support the hypothesis that differences in gross neuronal structure, perhaps even the subtle differences that distinguish subclasses of neurons in a given lamina, are predictive of underlying differences in the type and distribution of ion channels in the nerve cell membrane and connections of cells within the cortical circuit.

Amygdaloid projections to the frontal cortex and the striatum in the rat.

Abstract: Projections from the basolateral nucleus of the amygdala (BLA) to the frontal cortex and the striatum were studied by using Phaseolus vulgaris-leucoagglutinin (PHA-L) anterograde tracing technique in the rat. PHA-L injections into the rostral part of the BLA resulted in a dense labeling of fibers with boutons in the dorsal bank of the rhinal fissure and in the lateral and the medial agranular cortex. PHA-L injections into the caudal part of the BLA produced a dense labeling of fibers in the medial surface of the frontal cortex. In most of the cortical regions, labeled fibers were predominantly distributed in two bands: one in the deep part of layers I and II and the other, heavier band, in layers V and VI. PHA-L injections into the rostral BLA resulted in a dense labeling of fibers with boutons in the olfactory tubercle, the rostral and caudolateral portion of the nucleus accumbens, and a large region of the caudate-putamen. The labeled area of the caudate-putamen included the rostroventral area, the central area, and the area caudal to the anterior commissure and dorsal and lateral to the globus pallidus. PHA-L injections into the caudal BLA produced fiber labeling in the most rostromedial area of the caudate-putamen facing the lateral ventricle, the medial portion of the nucleus accumbens, and the lateral septum. In the rostroventral striatum, PHA-L-labeled fibers selectively innervated the matrix compartment that contains abundant somatostatin-immunoreactive fibers. Compartmental segregation was less clear in the caudodorsolateral caudate-putamen and in the nucleus accumbens. Electron microscopy revealed that PHA-L-labeled boutons in the striatum contained abundant, small, round vesicles. These boutons formed asymmetrical synapses with dendritic spines of striatal neurons.

Quantitative analysis of a vulnerable subset of pyramidal neurons in Alzheimer's disease: I. Superior frontal and inferior temporal cortex.

Abstract: Various cytoskeletal proteins have been implicated in the cellular pathology of Alzheimer's disease. A monoclonal antibody (SMI32) that recognizes nonphosphorylated epitopes on the medium (168 kDa) and heavy (200 kDa) subunits of neurofilament proteins has been used to label and analyze a specific subpopulation of pyramidal neurons in the prefrontal and inferior temporal cortices of normal and Alzheimer's disease brains. In Alzheimer's disease, the distribution of neuropathological markers predominates in layers III and V in these association areas. In these neocortical regions, SMI32 primarily labels the perikarya and dendrites of large pyramidal neurons, predominantly located within layers III and V. In Alzheimer's disease, a dramatic loss of SMI32-immunoreactive (ir) cells was observed, affecting particularly the largest cells (i.e., cells with a cross-sectional perikaryal area larger than 350 microns 2). The staining intensity of the largest SMI32-ir neurons was significantly reduced in Alzheimer's disease cases, suggesting that an inappropriate phosphorylation of these cytoskeletal proteins may take place in the course of the pathological process. In addition, the SMI32-ir neuron loss and total neuron loss were highly correlated with neurofibrillary tangle counts, whereas such a correlation was not observed with neuritic plaque counts. These quantitative data suggest that SMI32-ir neurons represent a small subset of pyramidal cells that share certain anatomical and molecular characteristics and are highly vulnerable in Alzheimer's disease. Other studies have suggested that SMI32-ir neurons are likely to furnish long corticocortical projections. Thus, their loss would substantially diminish the effectiveness of the distributed processing capacity of the neocortex, resulting in a neocortical isolation syndrome as reflected by the clinical symptomatology observed in these patients. Such correlations between the expression of a selective cellular pathology and specific elements of cortical circuitry will increase our understanding of the molecular and cellular characteristics underlying a given neuronal subclass vulnerability in Alzheimer's disease or other neurodegenerative disorders.