Ocular dominance columns and their development in layer IV of the cat's visual cortex: a quantitative study.
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Biomedical subjects
Publications and source records attributed to C J Shatz.
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1. The relation between the physiological pattern of ocular dominance and the anatomical distribution of geniculocortical afferents serving each eye was studied in layer IV of the primary visual cortex of normal and monocularly deprived cats. 2. One eye was injected with radioactive label. After allowing sufficient time for transeuronal transport, micro-electrode recordings were made, and the geniculocoritcal afferents serving the injected eye were located autoradiographically. 3. In layer IV of normal cats, cell were clustered according to eye preference, and fewer cells were binocularly driven than in other layers. Points of transition between groups of cells dominated by one eye and those dominated by the other were marked with electrolytic lesions. A good correspondence was found between the location of cells dominated by the injected eye and the patches of radioactively labelled geniculocortical afferents. 4. Following prolonged early monocular deprivation, the patches of geniculocortical afferents in layer IV serving the deprived eye were smaller, and those serving the non-deprived eye larger, than normal. Again there was a coincidence between the patches of radioactively labelled afferents and the location of cells dominated by the injected eye. 5. The deprived eye was found to dominate a substantial fraction (22%) of cortical cells in the fourth layer. In other cortical layers, only 7% of the cells were dominated by the deprived eye. 6. These findings suggest that the thalamocortical projection is physically rearranged as a consequence of monocular deprivation, as has been demonstrated for layer IVc of the monkey's visual cortex (Hubel, Wiesel & Le Vay, 1977).
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In Siamese cats, previous studies have shown that a genetic mutation causes retinogeniculate fibers in each eye which arise from the temporal retina representing the 20 degrees of ipsilateral visual field adjacent to the vertical meridian to cross aberrantly in the optic chiasm, thereby terminating in the wrong lateral geniculate nucleus. The abnormality is expressed subsequently at the level of the visual cortex. This paper presents anatomical evidence that the pattern of commissural visual connections in the "Boston" variety of Siamese cat also is highly abnormal in comparison to that of ordinary cats. The topographical distribution of neurons supplying visual fibers to the splenium of the corpus callosum was studied in Boston Siamese and ordinary cats using the method of retrograde transport of horseradish peroxidase (HRP) following localized cortical injections made through a recording micropipette. In ordinary cats, after an HRP injection at the border between cortical areas 17 and 18, which represents the vertical meridian of the visual field, HRP-labeled cells in areas 17 and 18 of the opposite hemisphere were found only immediately adjacent to the 17-18 border, thus confirming the results of previous investigations. In Boston Siamese cats, the border represents a region in the ipsilateral visual field roughly 20 degrees away from the vertical meridian, and the vertical meridian representation is displaced to sites within areas 17 and 18 proper. When HRP was injected at the 17-18 border, labeled cells in the opposite hemisphere were located well within area 17 near the suprasplenial sulcus, and also well within area 18; few labeled cells were found at the 17-18 border. When an HRP injection was placed at the vertical meridian representation, again few HRP-labeled cells were found at the opposite 17-18 border, but instead most were found in area 17 slightly medial to the border, and in area 18 slightly lateral to it. Thee findings were complemented in an autoradiographic study in which orthograde transport of tritiated proline after a localized cortical injection was used to demonstrate the distribution of callosal terminals. Thus the pattern of callosal connections revealed in Boston Siamese cats, although anatomically different from that of ordinary cats, was nevertheless consistent with the proposal that cortical sites representing similar visual field coordinates in each hemisphere are appropriately interconnected via the corpus callosum. The laminar distribution of callosal connections was examined briefly. Layer III pyramidal cells of areas 17 and 18 supplied the majority of terminals to the opposite 17-18 border. Pyramidal cells of Layers II and VI, and Layer IVa in area 18, made a smaller contribution. In areas 17 and 18, the same cortical layers (II, III, and VI; and IVa in 18) were again the major sites of callosal termination. A clear projection to the base of layer I was also noted. The laminar distribution of callosal connections in ordinary and Boston Siamese cats were not substantially different.
The dendritic form of a cell may be established by many factors both intrinsic and environmental. Blockade of action potentials along the course of axons and in their postsynaptic targets dramatically alters the development of axonal morphology. The extent to which blockade of target cell activity retrogradely alters the dendritic morphology of the presynaptic cells is unknown. To determine whether the establishment of dendritic form by developing retinal ganglion cells depends on activity within their targets, the sodium channel blocker, tetrodotoxin (TTX), was administered via minipumps to the diencephalon of cat fetuses from embryonic day 43 (E43) to E57. At E57 retinae were removed and living retinal ganglion cells injected in vitro with Lucifer yellow to reveal their dendritic morphology. In the TTX-treated animals both alpha and beta types of retinal ganglion cells were present, as were putative gamma cells. Overall, the dendrites of retinal ganglion cells in TTX-treated animals appeared qualitatively and quantitatively similar to those of untreated animals. The only significant change in the TTX-treated cases was a small increase in the number of dendritic spines on the non-beta cells. These results indicate that the acquisition of basic dendritic form of developing ganglion cells is not influenced by the action potential activity within their targets, and that it is also independent of the terminal branching patterns of their axons.
When connections are first formed during the development of the vertebrate nervous system, inputs from different sources are frequently intermixed and the specific adult pattern then emerges as the different inputs segregate from each other. During the prenatal development of connections between retina and lateral geniculate nucleus (LGN) in the cat, the projections from the two eyes initially overlap with each other within the LGN. Over the next 3 weeks a reduction in the amount of overlap occurs so that by birth, a segregated pattern similar to the adult is present. We report here that during the period of overlap, individual retinogeniculate axons are simple in shape and restricted in extent without any widespread branches. Further, the appearance of the segregated pattern of eye input is accompanied by the elaboration of extensive new axonal arbors within appropriate LGN territory accompanied by retraction of only a limited number of minor branches. This developmental strategy contrasts with that in other regions of the vertebrate central nervous system in which the orderly adult pattern of connections within a target is achieved by a relative reduction in the overall extent of the axon arbor.
In the development of the mammalian telencephalon, the genesis of neurons destined for the various layers of the cerebral cortex is preceded by the generation of a population of cells that comes to reside in the subplate and marginal zones (see ref. 2 for nomenclature). In the cat, these cells are present in large numbers during development, when their location is correlated with the arrival and accumulation of ingrowing axonal systems and with synapses. However, as the brain matures, the cells disappear and the white matter and layer 1 of the adult emerge. Their disappearance occurs in concert with the invasion of the cortical plate by the axonal systems and with the elimination of the synapses from the subplate. Here we report that the subplate cells have properties typical of mature neurons. They have the ultrastructural appearance of neurons and receive synaptic contacts. They also have long projections and are immunoreactive for MAP2 (microtubule associated protein 2). Further, subpopulations are immunoreactive for one of several neuropeptides. These observations suggest that during the fetal and early postnatal development of the mammalian telencephalon the subplate cells function as neurons in synaptic circuitry that disappears by adulthood.
The developing human cerebral cortex is distinguished by a particularly wide subplate, a transient zone in which crucial cell-cell interactions occur. To further understand the role of the subplate in human brain development, we have studied the immunohistochemical expression of certain neuronal (GAP-43, MAP-2, parvalbumin) and astroglial (vimentin, GFAP) markers in the developing visual cortex from gestational ages of 14 weeks to 9 months post-term. At 14-22 weeks, immunoreactivity to GAP-43, a protein involved in axonal outgrowth, was most prominent in the subplate and marginal zone neuropil and in the fibers of the radiations running near the ventricular zone; at 22-42 weeks, GAP-43 immunoreactive fibers were observed in the maturing cortical plate. Immunoreactivity for the microtubule-associated protein MAP-2 was present in the differentiating cortical plate at 14 weeks, but at 22-42 weeks was most prominent in the somata and dendrites of differentiated neurons, particularly the Cajal-Retzius neurons of the marginal zone, in neurons of the subplate and in those forming cortical layer 5. Parvalbumin immunoreactivity did not appear until 26 weeks, when stained neurons were in a sparse band of cells in layer 6 and upper subplate. Vimentin and GFAP did not stain differentiated neuronal cells. Vimentin immunoreactivity appeared early in neuroepithelial and radial glial cells, decreasing after 35 weeks, with a concomitant increase in GFAP immunoreactivity in radial glial and maturing astrocytic cells. Our results show that despite the greater complexity of the developing human neocortex, molecular markers are expressed in spatial and temporal patterns similar to those observed in non-human primates, carnivores and rodents. These protein markers should prove useful in developmental staging, and in providing a framework in which to examine congenital disorders of cerebral development.
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