A difference in hypothalamic structure between heterosexual and homosexual men.

The anterior hypothalamus of the brain participates in the regulation of male-typical sexual behavior. The volumes of four cell groups in this region [interstitial nuclei of the anterior hypothalamus (INAH) 1, 2, 3, and 4] were measured in postmortem tissue from three subject groups: women, men who were presumed to be heterosexual, and homosexual men. No differences were found between the groups in the volumes of INAH 1, 2, or 4. As has been reported previously, INAH 3 was more than twice as large in the heterosexual men as in the women. It was also, however, more than twice as large in the heterosexual men as in the homosexual men. This finding indicates that INAH is dimorphic with sexual orientation, at least in men, and suggests that sexual orientation has a biological substrate.

Retrograde transneuronal transport of wheat-germ agglutinin to the retina from visual cortex in the cat.

Injections of peroxidase-conjugated wheat-germ agglutinin (WGA-HRP) were made into areas 17 or 18 of cats. After survivals of 3-7 days, foci of HRP-labeled ganglion cells were found at the appropriate topographic locations in the retinas. The labeling was interpreted as resulting from retrograde transneuronal transport through the lateral geniculate nucleus. This phenomenon offers a new and simple technique for the study of retinotopic maps in visual cortex.

Morphological and immunocytochemical observations on the visual callosal projections in the cat.

The connections between the left and right 17-18 border regions of the cat's visual cortex were labeled by axonal transport of peroxidase-conjugated wheat-germ agglutinin (WGA-HRP) and examined by light and electron microscopy. The cells of origin of the pathway were further characterized by transport of fluorescent microspheres ("beads") followed by in vitro injection of cells with Lucifer Yellow, and by beads transport followed by immunocytochemistry with antibodies to gamma-aminobutyric acid (GABA). The cells of origin of the callosal pathway were located in the lower part of layer 2/3, the upper part of layer 4, and layer 6. In layers 2/3 and 6, they were pyramidal cells; in layer 4 they were star pyramids or spiny stellate cells. None of them were spinefree or sparsely spinous cells, and none were GABA-positive. The axon terminals of the callosal pathway formed type 1 (asymmetric) synapses, and most of them contacted dendritic spines. Both the cells of origin and the terminals were arranged in patches. The findings suggest that the direct action of the callosal pathway is excitatory. The callosal system appears to represent only a subset of the cell types that have intrinsic horizontal projections within areas 17 or 18.

Patchy intrinsic projections in visual cortex, area 18, of the cat: morphological and immunocytochemical evidence for an excitatory function.

Small injections of peroxidase-labeled wheat germ agglutinin into cat area 18 gave rise to patches of labeled cells and axon terminals around the injection site. In EM sections it was found that the labeled cells had a pattern of synaptic inputs characteristic of spiny-dendrite neurons (pyramidal or spiny stellate cells). The labeled axon terminals formed type 1 (asymmetric) synapses, most of which were made onto dendritic spines. In other experiments injections of fluorescent beads were made into area 18, giving rise to a similar patchy distribution of labeled cells. The sections were then processed for immunocytochemical demonstration of gamma-aminobutyric acid (GABA). The bead-labeled cells in the patches were GABA negative. The findings suggest that the patchy projections mediate mutual excitation between groups of spiny-dendrite neurons.

Ocular dominance and disparity coding in cat visual cortex.

The orientation selectivity, ocular dominance, and binocular disparity tuning of 272 cells in areas 17 and 18 of barbiturate-anesthetized, paralyzed cats were studied with automated, quantitative techniques. Disparity was varied along the axis orthogonal to each cell's best orientation. Binocular correspondence was established by means of a reference electrode positioned at the boundary of lamina A and A1 in the area centralis representation of the lateral geniculate nucleus. Measures were derived that expressed each cell's disparity sensitivity and best disparity and the shape and slope of its tuning curve. Cells were found that corresponded to categories described by previous authors ("disparity-insensitive," "tuned excitatory," "near," and "far" cells), but many others had intermediate response patterns, or patterns that were difficult to categorize. Quantitative analysis suggested that the various types belong to a continuum. No relationship could be established between a cell's best orientation and its ocular dominance or any aspect of its disparity tuning. There was no relationship between a cell's ocular dominance and its sensitivity to disparity. Ocular dominance and best disparity were related. As reported by others, cells with best disparities close to zero (the fixation plane) tended to have balanced ocularity, while cells with best disparities in the near or far range had a broad distribution of ocular dominance. Among cells with receptive fields near the vertical meridian, those preferring far disparities tended to be dominated by the contralateral eye, and those preferring near disparities by the ipsilateral eye. It is suggested that this relationship follows from the geometry of near and far images and the pattern of decussation in the visual pathway. There was a significant grouping of cells with similar best disparities along tangential electrode tracks. We believe that this grouping is due to the columnar organization for ocular dominance and the relationship between ocular dominance and best disparity. No evidence was found for a columnar segregation of disparity-sensitive and disparity-insensitive cells.

Functional organization of primary visual cortex in the mink (Mustela vison), and a comparison with the cat.

The functional organization of geniculocortical afferents and the visual responses of neurons in primary visual cortex (area 17) were studied in barbiturate-anesthetized, paralyzed minks and cats. Responses of the afferents were studied after silencing intrinsic cortical activity with injections of kainic acid. In both species, afferents were segregated into patches on the basis of eye of origin. In the mink, but not in the cat, there was a further segregation on the basis of center type, with on- and off-center afferents terminating in alternating, partially overlapping patches. The visual responses of cortical neurons in the mink showed many similarities to those in the cat. Nearly all units were orientation-selective, and there was a columnar organization for preferred orientation. Many units were selective for one direction of movement. Within the binocular segment of cortex, although many units could be driven from either eye, there was a marked bias toward the contralateral eye compared to the cat. There was a columnar system for ocular dominance, but contralateral eye columns were wider than ipsilateral. In both species, a quantitative study was made of the responses of cortical neurons to stationary, flashing slits as a function of position in the receptive field. In the mink, and less clearly in the cat, units could be identified as simple or complex on the basis of the spatial separation or overlap of "on" and "off" discharge zones. In both species, simple cells were found most commonly in layers IV and VI, while layer V contained the greatest proportion of complex cells. The relative strengths of the on and off discharges of single cells were also measured. In the mink, many units gave better overall responses to the on or off phase of the stimulus, and 15% showed a strong (greater than 9:1) preference for one or the other, compared to 4% in the cat. In the mink, units with a common preference for the on or off phase of stationary stimuli were arranged in columnar aggregates, a feature of cortical organization that was not found in the cat. These columns probably result from the partial segregation of on-center and off-center geniculate afferents within layers IV and VI of the mink's cortex. On-dominated columns were, however, wider or more numerous than off-dominated columns.

Synaptic organization of claustral and geniculate afferents to the visual cortex of the cat.

Claustral and geniculate afferents to area 17 were labeled by anterograde axonal transport of peroxidase-conjugated wheatgerm agglutinin, and examined in the electron microscope. A peroxidase reaction protocol that led to labeling in the form of minute holes in the EM sections was used. Both types of afferents formed type 1 (presumed excitatory) synapses exclusively. In agreement with previous reports the great majority of geniculate afferents to layers 4 and 6 contacted dendritic spines. The claustral afferents to layers 1 and 6 also predominantly contacted spines. In layer 4, however, claustral afferents contacted spines and dendritic shafts about equally. The results suggest a substantial claustral input to smooth-dendrite cells in layer 4, which are thought to be inhibitory in function. This may be the circuit by which the claustrum helps to generate end-stopped cortical receptive fields (Sherk and LeVay, 1983).

Laminar and synaptic organization of the projection from the thalamic nucleus centralis to primary visual cortex in the cat.

The projection from the nucleus centralis (an intralaminar thalamic nucleus) to the primary visual cortex was examined with anterograde and retrograde tracing techniques. After large injections of horseradish peroxidase into areas 17 and 18 almost one-half of the neurons in the nucleus centralis were retrogradely labeled. An injection of 3H-proline into the nucleus centralis led to sparse anterograde labeling in layers 5 and 6 of areas 17 and 18. Large injections of peroxidase-conjugated wheat germ agglutinin (WGA) into the nucleus centralis led to similar anterograde labeling of layers 5 and 6 and, in addition, to a band in layer 1. No retrogradely labeled cells were seen in areas 17 or 18. The WGA-labeled terminals in area 17 were examined in the electron microscope: they formed type 1 (asymmetric) synapses on dendritic spines. These observations suggest that the afferents from the nucleus centralis primarily contact pyramidal cells that project to subcortical targets. The findings are consistent with physiological studies suggesting that the nucleus centralis is involved in the modulation of cortical outflow with varying levels of arousal.

Anatomical organization of the visual system of the mink, Mustela vison.

The organization of the retinogeniculocortical visual system of the mink was studied by anterograde and retrograde tracer techniques, by physiological mapping, and by direct recordings from axonal terminals after injection of kainic acid. In the lateral geniculate nucleus, retinogeniculate afferents are segregated according to eye of origin between the two principal layers, A and A1. Within each of these layers there is a further parcellation according to functional type: on-center afferents terminate in the anterior leaflets of A and A1, and off-center afferents in the posterior leaflets. This separation is preserved in area 17: geniculocortical afferents terminate in ocular dominance patches in layer IV, and these patches coexist with an alternating, partially overlapping set of patches for on-center and off-center inputs that we have demonstrated previously (McConnell and LeVay: Proc. Natl. Acad. Sci. USA 81:1590-1593, '84). In both the lateral geniculate nucleus and in area 17, the contralateral eye predominates to a much greater extent than in the cat. Visual cortical areas corresponding to the cat's areas 17, 18, and 19 can be identified in the mink, but they are shifted posterolaterally in the hemisphere, and they show less emphasis on the representation of central retina. Mapping studies also revealed the existence of a fourth visual area in the splenial sulcus (area SV) adjacent to the representation of the far periphery in area 17. This area differs from the corresponding region in the cat in that it receives direct projections from the lateral geniculate nucleus and from areas 17 and 18. The lateral geniculate nucleus projects to each of the four cortical areas that were mapped. The bulk of the projection to area 17 is derived from the principal layers, A and A1, while most cells projecting to areas 18 and SV are found in the C-layer complex. The recurrent projection from area 17 to the lateral geniculate nucleus arises from pyramidal neurons in layer VI, and terminates through all layers of the lateral geniculate nucleus, but most densely in the interlaminar zones. Areas 18 and SV project predominantly to the C layers. Areas 17, 18, and SV are reciprocally connected with the claustrum and the LP-pulvinar complex, and project to the superior colliculus. All four visual cortical areas are mutually interconnected; these associational projections arise from both the supragranular and infragranular layers.

Topographic organization of the optic radiation of the cat.

Pairs of injections of different neuroanatomical tracers--peroxidase-conjugated wheat-germ agglutinin (WGA) and [3H]proline--were made into the lateral geniculate nucleus (LGN) of the cat, and the course of the labeled fibers in the optic radiation was reconstructed. When the two injections were widely separated in the rostrocaudal dimension of the LGN (i.e., one in the representation of the lower quadrant of the visual field and one in the upper quadrant), the two sets of labeled fibers also remained separated in the long (roughly rostrocaudal) axis of the optic radiation. When the injections were widely separated in the mediolateral dimension of the LGN (i.e., one at the representation of the area centralis and one on the horizontal meridian in the far periphery of the field), the two sets of labeled fibers were separated in the short (mediolateral) dimension of the radiation. Shortly before reaching area 17, however, the medially and laterally placed fibers exchanged positions. This crossing is the basis of the topological inversion in the optic radiation deduced previously by Connolly and Van Essen (J. Comp. Neurol. 226:544-564, '84). The retinotopic organization of fibers in the radiation is less precise (in either dimension) than that of their terminal arborizations in visual cortex, but even injections as close as 1 mm to each other gave rise to spatially distinct fiber distributions. The WGA injections also labeled the corticogeniculate fibers by retrograde transport; these fibers traveled in a separate pathway medial to the optic radiation.

The complete pattern of ocular dominance stripes in the striate cortex and visual field of the macaque monkey.

Ocular dominance stripes in the striate cortex of a macaque monkey were labeled by autoradiography after injection of [3H]proline into one eye. The stripes were reconstructed on a representation of the flattened cortical surface by two independent techniques: one used computer graphics, and the other was the manual unfolding procedure of Van Essen and Maunsell (VanEssen, D. C., and J. H. R. Maunsell (1980) J. Comp. Neurol. 191: 255-281). The two reconstructions differed in many details of the pattern but were in agreement on its general features. As described in earlier studies, the stripes formed a system of parallel bands, with numerous branches and islands. They were roughly orthogonal to the V1/V2 border throughout the binocular segment of the cortex. In the lateral part of the operculum, where the fovea is represented, the stripes were less orderly than elsewhere. In the calcarine fissure the stripes ran directly across the striate cortex from its dorsal to its ventral margin. In the far periphery the stripes for the ipsilateral eye became progressively narrower, eventually fragmenting into small islands at the edge of the monocular segment. The overall periodicity (width of a left- plus right-eye pair of stripes) averaged 0.88 mm but decreased by a factor of about 2 from center to periphery. This decrease was not accounted for solely by shrinkage of the ipsilateral eye stripes. The flattened cortical reconstruction was transformed back into visual field coordinates, using information about visual field topography obtained from the detailed mapping study of Van Essen et al. (Van Essen, D.C., W.T. Newsome, and J.H.R. Maunsell (1984) Vision Res. 24: 429-448), as well as from more limited mapping done in the same monkey that was used for the reconstruction. In the transformed map, the stripes increased in width about 40-fold from the fovea to the far periphery. As deduced previously (LeVay, S., D. H. Hubel, and T. N. Wiesel (1975) J. Comp. Neurol. 159: 559-576; Hubel, D. H., and D. C., Freeman (1977) Brain Res. 122: 336-343), there were portions of the map in which the stripes followed curves approximating isoeccentricity lines, but this relationship was not very exact or consistent. The pattern of stripes appears to be more meaningfully related to the geometry of the cortical surface. This has significant implications for understanding the developmental mechanisms involved in stripe formation.

Effects of strabismus and monocular deprivation on the eye preference of neurons in the visual claustrum of the cat.

Visual response properties of neurons in the dorsocaudal claustrum were studied in two cats reared with convergent strabismus and three cats reared with monocular lid-suture. In the normal claustrum, most cells respond about equally well to stimulation of either eye (Sherk and LeVay, '81). In the strabismic animals, there was a partial breakdown of binocularity: most cells remained binocular but were influenced more strongly by one eye (usually the contralateral eye) than the other. The loss of binocularity was less extreme in the claustrum than in area 17 of the same animals. In the monocularly deprived cats, claustral cells responded exclusively to the experienced eye. We interpret the changes observed in the claustrum as reflecting changes in the ocular dominance of cortical inputs to the claustrum, rather than as evidence for plasticity within the claustrum itself. Autoradiography was used to study the return projection from claustrum to cortex in monocular deprivation. The cortical labeling pattern resembled that seen in normal cats. To examine whether this return projection might be involved in reducing cortical responsiveness to the deprived eye, recordings were made from area 17 of a monocularly deprived cat before and after ablation of the ipsilateral claustrum by injection of kainic acid. Following ablation, there was no unmasking of cortical responses to the deprived eye. Thus the cortico-claustral loop does not appear to suppress cortical responses to the deprived eye.

Segregation of on- and off-center afferents in mink visual cortex.

In the lateral geniculate nucleus of the mink, on-center and off-center neurons occupy separate layers [LeVay, S. & McConnell, S.K. (1982) Nature (London) 300, 350-351]. To study the mode of termination of geniculate afferents in area 17, we recorded from their terminal arborizations in layer IV after the destruction of cortical neurons by injection of kainic acid. At the majority of recording sites, multifiber responses were entirely or predominantly of one type: on-center or off-center. Responses obtained during perpendicular penetrations showed the same preferred sign of contrast throughout the thickness of layer IV. During tangential penetrations through the layer, we encountered sequences of on- and off-center activity separated by stretches of mixed responses. We conclude that on- and off-center afferents terminate in separate, alternating patches that occupy the full thickness of layer IV. These coexist with another set of patches in which the same afferents are segregated by eye of origin.

Contribution of the cortico-claustral loop to receptive field properties in area 17 of the cat.

The contribution of the cat's claustrum to the response properties of cells in area 17 was studied by destroying the left claustrum and examining receptive field properties of cells in both the left and right area 17. For each cell we assessed sharpness of orientation tuning, degree of direction selectivity, length summation, end-stopping, ocular dominance, responsiveness, and several other properties. On the lesioned side, 462 cells were studied, and on the control side, 636 cells. All cats showed a reduction in the number of end-stopped cells in area 17 on the side of the lesion. This was particularly marked in layers 2 + 3 and 4, where end-stopped cells are normally most abundant. In the control hemisphere, 43% of the sample from these layers showed at least moderate end-stopping whereas, in contrast, only 21% exhibited this degree of end-stopping on the side of the lesion. There was no obvious change in other response properties. We conclude that one function of the cat's claustrum is to help regulate the length selectivity of cells in area 17.