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C J Shatz

Publications and source records attributed to C J Shatz.

At least 91 records · Page 5Linked to original sources

A fibronectin-like molecule is present in the developing cat cerebral cortex and is correlated with subplate neurons.

The subplate is a transient zone of the developing cerebral cortex through which postmitotic neurons migrate and growing axons elongate en route to their adult positions within the cortical plate. To learn more about the cellular interactions that occur in this zone, we have examined whether fibronectins (FNs), a family of molecules known to promote migration and elongation in other systems, are present during the fetal and postnatal development of the cat's cerebral cortex. Three different anti-FN antisera recognized a single broad band with an apparent molecular mass of 200-250 kD in antigen-transfer analyses (reducing conditions) of plasma-depleted (perfused) whole fetal brain or synaptosome preparations, indicating that FNs are present at these ages. This band can be detected as early as 1 mo before birth at embryonic day 39. Immunohistochemical examination of the developing cerebral cortex from animals between embryonic day 46 and postnatal day 7 using any of the three antisera revealed that FN-like immunoreactivity is restricted to the subplate and the marginal zones, and is not found in the cortical plate. As these zones mature into their adult counterparts (the white matter and layer 1 of the cerebral cortex), immunostaining gradually disappears and is not detectable by postnatal day 70. Previous studies have shown that the subplate and marginal zones contain a special, transient population of neurons (Chun, J. J. M., M. J. Nakamura, and C. J. Shatz. 1987. Nature (Lond.). 325:617-620). The FN-like immunostaining in the subplate and marginal zone is closely associated with these neurons, and some of the immunostaining delineates them. Moreover, the postnatal disappearance of FN-like immunostaining from the subplate is correlated spatially and temporally with the disappearance of the subplate neurons. When subplate neurons are killed by neurotoxins, FN-like immunostaining is depleted in the lesioned area. These observations show that an FN-like molecule is present transiently in the subplate of the developing cerebral cortex and, further, is spatially and temporally correlated with the transient subplate neurons. The presence of FNs within this zone, but not in the cortical plate, suggests that the extracellular milieu of the subplate mediates a unique set of interactions required for the development of the cerebral cortex.

Animals↗

Dendritic growth and remodeling of cat retinal ganglion cells during fetal and postnatal development.

We have studied the development of retinal ganglion cell morphology in the cat's visual system from early fetal to postnatal times. In particular, we have examined the contribution of growth and remodeling to the establishment of mature retinal ganglion cell form. Ganglion cells were identified by retrograde labeling with rhodamine latex microspheres deposited in the superior colliculus and lateral geniculate nucleus between embryonic day 34 (E34; birth = E65) and adulthood. To reveal the fine morphological details of retrogradely labeled ganglion cells, 48 hr later Lucifer yellow was injected intracellularly in living retinae that had been dissected and maintained in vitro. Our results show that at E35-37 the majority of ganglion cells are very simple in morphology, with a few dendritic processes that are generally aligned in a radial direction towards or away from the optic disc. During the ensuing 2 week period, there is a progressive growth and elaboration of dendrites. By E50, some ganglion cells resembling the adult alpha, beta, and gamma classes can be identified based on comparisons of the appearance and dimensions of their dendritic trees and somata with neighboring filled cells. However, ganglion cell dendrites and axons at this age express several transient morphological features. The axons of ganglion cells give rise to delicate processes originating from the intraretinal portion of the axon, including side branches, present in about half of the cells, and occasionally bifurcations that give rise to axon collaterals. These transient axonal features are present throughout development, including the neonatal period; no axon collaterals were observed after postnatal day 15, while axonal side branches persisted even at P31 but were gone by adulthood. Ganglion cell dendrites exhibit excessive branches and exuberant somatic and dendritic spines. Quantitative analysis of these processes shows that after E45 dendritic trees increase dramatically in complexity, reaching the peak number of spines and branch points by the first week of postnatal life. The number of dendritic processes then falls abruptly to reach near-adult levels by the end of the first postnatal month. Even though dendritic morphology closely resembles that seen in the adult at this age, ganglion cell bodies and dendrites must continue to grow to reach their adult size.(ABSTRACT TRUNCATED AT 400 WORDS)

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Transient morphological features of identified ganglion cells in living fetal and neonatal retina.

The function and morphology of retinal ganglion cells in the adult mammalian visual system has been well studied, but little is known about how the adult state is achieved. To address this question, the morphological changes that retinal ganglion cells undergo during development were studied. Ganglion cells were first identified by retrograde labeling with rhodamine latex microspheres deposited in retinorecipient targets in fetal and early postnatal cats. The structure of ganglion cells was then revealed by intracellular injection of Lucifer yellow in living retinas removed and maintained in vitro. As early as 2 weeks before birth, a morphologically diverse assortment of ganglion cells is present, some of which resemble the alpha, beta, and gamma classes found in the adult. However, in contrast to the adult, developing ganglion cells exhibit several transient features, including excessive axonal and dendritic branching and exuberant somatic and dendritic spines. These morphological features indicate that there is a transient network of connectivity that could play an important role in the final determination of retinal ganglion cell form and function.

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Axon trajectories and pattern of terminal arborization during the prenatal development of the cat's retinogeniculate pathway.

In this study we have examined the trajectories taken by populations of ganglion cell axons and the spatial gradients of terminal arbor maturity within the lateral geniculate nucleus (LGN) during the prenatal development of the cat's visual system. To do so, an in vitro method of labeling optic tract axons from fetal brains between embryonic day 37 (E37) and postnatal day 2 (P2) with horseradish peroxidase (HRP) was used. At the earliest ages studied (E37-E53), optic axons leave the optic tract to run across the LGN toward their sites of termination in straight trajectories parallel to each other. At later ages (E57-P2), however, axons with abrupt changes in their course across the nucleus can be clearly identified. When the detailed terminal arbor morphology of the set of retinogeniculate axons filled with HRP at a given age was examined, two different spatial gradients of maturation could be detected. The terminal arbors of axons within LGN layer A are always more mature than those ending in layer A1, an observation consistent with previous findings that axons from the contralateral eye arrive within the LGN several days before those from the ipsilateral eye. Moreover, the terminal arbors of axons projecting to the medial portions of each layer are always more mature than their more lateral counterparts. These gradients are likely to be a direct reflection of the central-first, peripheral-last gradient associated with the neurogenesis of the retinal ganglion cells themselves. In the oldest animals studied (E58-P2), a remarkable periodic pattern of terminal arbor labeling was seen following a localized HRP injection into the optic tract. Within the labeled portions of the LGN, densely filled axon terminal arbors are separated by unlabeled gaps of similar width. This pattern of labeling could reflect local topographic disorder within the optic tract or could arise if axons of different classes of retinal ganglion cells run in separate portions of the optic tract. Taken together, all of these observations suggest that there may be a fair degree of topographic order in the retinogeniculate projection within the cat's LGN early on in development. However, when topographic errors are present, some can be corrected by minor readjustments in axonal trajectories.

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Prenatal development of cat retinogeniculate axon arbors in the absence of binocular interactions.

During prenatal development of the cat's retinogeniculate projection, inputs from the ganglion cell axons of the two eyes are initially intermixed with each other within the lateral geniculate nucleus (LGN). As development proceeds, the inputs sort out to give rise to the eye-specific layers characteristic of the adult. During this sorting out process, individual axons undergo a stereotyped sequence of morphological changes that ultimately produce the characteristic pattern of arborization in which axon arbors are restricted in extent only to those layers of the LGN appropriate for the eye of origin (Sretavan and Shatz, 1984, 1986). Here, we examine whether binocular interactions between retinal ganglion cell axons from the two eyes are required for the formation of this restricted pattern of terminal arborization. To examine this question, one eye was removed at embryonic day 23 (E23), when ganglion cell axons have not yet reached the optic chiasm, and the ganglion cell axons from the remaining eye were allowed to develop in the complete absence of binocular interactions. At E59, when segregation into eye-specific layers is normally almost complete, the retinogeniculate projection from the remaining eye was then examined both by anterograde transport following intraocular injections of 3H-leucine and by the in vitro filling of individual ganglion cell axons with HRP. Results from the intraocular injections showed that in the absence of one eye, the remaining eye is still capable of forming both ipsilateral and contralateral optic tracts; however, the projection was distributed diffusely throughout each LGN, rather than being confined to normal eye-specific territories. When individual HRP-filled axons were reconstructed and examined, it was remarkable to find that the pattern of terminal arborization was virtually indistinguishable from normal axons. As usual, arbors were restricted to the distal portion of each axon trunk, and measurements showed that the total linear length of axon contributing to each arbor was within the normal range (enucleated, 2310 +/- 920 microns; normal, 2520 +/- 810 microns). Furthermore, the terminal arborizations of axons appeared to be organized into a series of tiers within the LGN in a pattern surprisingly similar to the pattern of eye-specific layers normally present by E59. Also unchanged was the normally occurring loss of axons from the remaining optic nerve: Counts at E59 showed that about 2.3 X 10(5) axons were present in enucleated animals as compared to 2.5 X 10(5) axons in controls.(ABSTRACT TRUNCATED AT 400 WORDS)

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Development of glutamic acid decarboxylase immunoreactivity in the cat's lateral geniculate nucleus.

The development of glutamic acid decarboxylase (GAD) immunoreactivity in the cat's dorsal LGN was studied during fetal and postnatal life. In the adult, inhibitory interactions within the LGN are known to be mediated by GABA. Here we have used an antiserum to GAD, the rate-limiting synthetic enzyme for GABA, to examine the development of the anatomical substrate for this inhibitory system. The pattern of immunostaining observed in the adult cat LGN was similar to that reported by Fitzpatrick et al. (1984), with heavily stained somata and proximal dendrites located within the LGN layers and the adjacent perigeniculate nucleus (PGN). The LGN also contained a complex array of terminal staining. In development, specific staining was seen about 2 weeks before birth and was confined to PGN somata and, to a lesser extent, to somata located in the future ventral C-layers. A similar pattern of immunostaining was seen using GABA antiserum. Not until birth did the A-layers of the LGN show appreciable staining of both somata and terminals; however, even then the pattern of immunostaining was far from mature. Furthermore, excessive numbers of PGN neurons appeared to stain. By 5 weeks after birth, the intensity of both soma and terminal staining within the A-layers of the LGN increased substantially relative to that of the PGN and ventral C-layers. The first glomerular clusters of terminal staining could also be seen, and the number of stained PGN neurons had diminished to levels similar to those seen in the adult. The pattern of immunostaining was almost adultlike by 2 months after birth, except within the C-complex, where the staining did not yet show the distinct difference in staining intensity present in the adult between dorsal layer C and ventral layers C1 and C2. The final adult pattern of GAD immunoreactivity appeared by 3 months after birth. These results suggest that during fetal life the PGN and ventral C-layers of the LGN may supply the first source of GABA-mediated inhibition to the nucleus, with the major portion of the inhibition supplied by intrinsic LGN neurons arising postnatally. Thus, PGN neurons may provide part of the anatomical substrate for the inhibitory interactions seen physiologically during late fetal development (Shatz and Kirkwood, 1984). Finally, the relatively late appearance of the adultlike pattern of GAD immunostaining suggests that intrageniculate inhibitory circuitry continues to develop well after birth.

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The relationship between the geniculocortical afferents and their cortical target cells during development of the cat's primary visual cortex.

To study the prenatal development of connections between the lateral geniculate nucleus (LGN) and the primary visual cortex in the cat, we have examined the relationship between the position of ingrowing afferents from the LGN and their target cells in cortical layers 4 and 6 at various times during the cat's 65 d gestation period and during the first 3 weeks of postnatal life. In 1 series of experiments, the method of transneuronal transport of intraocularly injected tritiated proline (3H-proline), followed by autoradiography, was used to label the developing geniculocortical pathway. In another series, the tritiated thymidine (3H-thymidine) method was employed to keep track of the cells destined for layers 4 and 6 by labeling them on their birthdates (layer 4: embryonic day (E) 37-43; layer 6: E31-36) (Luskin and Shatz, 1985b) and then charting their locations at subsequent times during development. The results of the 2 sets of experiments were compared at corresponding ages. By E39, many of the cells of cortical layer 6 have completed their migrations and are situated within the cortical plate immediately above the subplate. However, the transneuronal labeling pattern indicates that the geniculocotical afferents have not yet arrived within the vicinity of the future visual cortex, but rather are still en route and confined within the optic radiations of the telencephalon. By E42, a week after the first afferents can be detected in the radiations, substantial transneuronal label is found in the subplate immediately below future visual cortex. However, the overlying cortical plate is free of label. Over the next 2 weeks, geniculocortical axons continue to accumulate in the subplate zone, and, in addition, transneuronal label can be found in the marginal zone. By E55 a faint geniculocortical projection can be detected within the cortical plate, but only within its deeper half (future layers 5 and 6), and even then the major portion of the projection is still confined to the subplate. The absence of a projection to cortical layer 4 at these ages is remarkable in view of the results from our 3H-thymidine experiments, which indicate that by E57 the majority of cells destined to belong to layer 4 have already completed their migrations and assumed positions superficial to the cells of layers 5 and 6. By birth, a substantial geniculocortical projection to cortical layer 4 can be detected in the transneuronal autoradiographs.(ABSTRACT TRUNCATED AT 400 WORDS)

Afferent Pathways↗

Prenatal development of retinal ganglion cell axons: segregation into eye-specific layers within the cat's lateral geniculate nucleus.

The morphological changes in individual retinal ganglion cell axons associated with the formation of the eye-specific layers in the dorsal lateral geniculate nucleus (LGN) were studied during the prenatal development of the cat's visual system. Previous work has shown that the pattern of segregated eye inputs found in the adult arises from an immature state in which inputs from the two eyes are intermixed within the nucleus (Shatz, 1983). Here, this developmental process is examined at its fundamental unit of connectivity--the individual retinal ganglion cell axon. To do so, an in vitro method was used to label fetal cat optic tract axons with HRP at various times during development between embryonic day 38 (E38) and postnatal day 2 (P2) (gestation = 65 d). The results presented here are based on reconstructions of 172 axons. During the initial period of intermixing (E38-43), axons are relatively simple in morphology. Many axons studied at the earliest ages (E38) end in growth cones and have very few branches along the main axon trunk as they traverse the nucleus. By E43, the number of side branches given off along the main axon trunk has increased and most axons also have a simple terminal arbor. Over the next 2 weeks (E43-55), the majority of axons are studded with side branches and the terminal arbor is well defined. Then, between E55 and birth, axons lose their side branches and the eye-specific layers appear. By birth, nearly all axons have a smooth trunk and an elaborate terminal arbor restricted to the LGN layer appropriate to the eye of axon origin. When the number of side branches per axon was quantified, the time course of appearance and subsequent loss of side branches was found to parallel the time course of the initial intermixing of inputs and subsequent reduction in territory shared by the two eyes as determined from previous intraocular injection experiments. Our results also showed that the side branches along each axon were located primarily within LGN territory destined to be occupied by the other eye. Thus, the side branches are likely to represent a morphological substrate for the intermixing of inputs from the two eyes. These observations suggest that the segregation of eye input to the LGN involves two fundamental and simultaneous events. One event is the remodeling of the branching pattern along the length of the main axon trunk so that the side branches present early on are eliminated and the main axon trunk becomes smooth.(ABSTRACT TRUNCATED AT 400 WORDS)

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Neurogenesis of the cat's primary visual cortex.

The 3H-thymidine method of birth-dating was used to determine when the cells belonging to each of the principal cellular layers of the cat's primary visual cortex are generated. In order to detect systematic differences in the position of radioactively labeled cells following 3H-thymidine administration at different prenatal ages, a geometric method was devised to represent the distribution of labeled cells in the form of depth histograms. Results show that visual cortical neurogenesis occurs largely during the second half of gestation between embryonic day 31 (E31) and E57. Cells of layer 6 are generated early, between E31 and E38, whereas cells destined for successively more superficial layers are generated at progressively later times. Layer 4 cells, the principal targets of geniculocortical afferents, are generated between E37 and E44. In addition, a special population of cells embedded in the white matter below layer 6 was found to be produced throughout the week-long period immediately prior to the onset of layer 6 neurogenesis. Overall, this radial pattern of cortical neurogenesis closely resembles the inside-first, outside-last, spatiotemporal sequence of development described for the monkey's primary visual cortex (Rakic, '74). In addition to finding this pronounced gradient in the radial dimension, we were also able to detect a less pronounced gradient along the tangential dimension: neurons destined for any given layer in the anterior part of the cortex (inferior visual field representation) are generated slightly in advance of neurons destined for more posterior regions (superior visual field). However even our more quantitative histogram analysis failed to reveal a mediolateral (central to peripheral visual field) gradient within area 17. In the cat, layers 6, 5, and 4 each take about a week to be generated, although their total cell numbers and packing densities differ in the adult. About 2 weeks are required to produce the cells of layers 2 and 3 combined. Furthermore, we found that neurons belonging to different layers and different morphological classes can be generated simultaneously. This suggests that the identity of a cortical neuron is not solely a function of the time of neurogenesis.

Age Factors↗

Abnormal development of the retinogeniculate projection in Siamese cats.

In the visual system of Siamese cats, the lateral geniculate nucleus (LGN) receives an abnormally large projection from the contralateral eye and a correspondingly reduced projection from the ipsilateral eye. In order to determine how this abnormal pattern of retinal input arises, the prenatal development of the retinogeniculate projection was studied in Siamese cats using the anterograde transport of intraocularly injected [3H]leucine and horseradish peroxidase. Labeled axons from the ipsilateral eye can be detected in the optic tract by embryonic day 30 (E30; gestation is 65 days), several days later than found in normally pigmented animals. The ipsilateral projection is not only apparently delayed but also is reduced in size as compared with normal animals, and this reduction persists throughout development, indicating that the Siamese mutation acts to misdirect growing optic axons to the contralateral side of the brain as originally proposed (Guillery, R. W. (1969) Brain Res. 14: 739-741). The effect of an altered retinal projection on the ingrowth and segregation of retinal fibers to the LGN was also examined. In Siamese fetuses, not until E41 can significant label be seen within the ipsilateral LGN as compared to E35 in normally pigmented fetuses. As in normal animals, in Siamese fetuses, also, the labeled retinogeniculate afferents from the two eyes initially overlap within regions of the LGN before segregating into layers. However, measurements of the area occupied by labeled afferents from the ipsilateral and contralateral eyes indicate that maximum overlap of the two sets of afferents, although close to normal in amount, does not occur until about E51--again several days later than in normally pigmented animals (E47). The time course of segregation is also altered in Siamese cats. The onset of segregation, as signaled by the removal of contralateral eye afferents from territory destined for the ipsilateral eye and by the restriction of ipsilateral eye afferents, does not occur until about E51 in Siamese cats as compared with E47 in normally pigmented animals. Despite this delay in onset, the final segregation of the two sets of afferents in Siamese cats reaches adult-like levels at about the normal time. Thus, the misrouting of axons at the optic chiasm in Siamese cats not only alters the final pattern of innervation from the two eyes within the LGN, but also delays the onset and shortens the total duration of segregation itself.

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Studies of the earliest generated cells of the cat's visual cortex: cogeneration of subplate and marginal zones.

The earliest generated cells of the cat's telencephalon that may play a role in the formation of the primary visual cortex are the subject of this study. Using [3H]thymidine autoradiography, we have found that these cells are generated between embryonic day 24 (E24) and E30 (gestation is 65 days) and that they are present in very low numbers in the white matter of the adult brain. These cells are rarely labeled by injections made after E30, when the cells destined for the cortical layers are generated. Examination of the labeling pattern in the fetal brain 10 days or more after administration of [3H]thymidine between E24 and E30 revealed a bistratified distribution of these early generated cells. Labeled cells were found in large numbers in two embryonic zones flanking the developing cortical plate: above in the marginal zone and below in the subplate. (Some if not all of the marginal zone cells constitute the population of Cajal-Retzius cells of the cat's telencephalon.). These experiments indicate that cells of the subplate and marginal zones are cogenerated in time during the days just preceding the genesis of the cortical plate. We also examined the distribution of the early generated cells shortly after their genesis--on E30, a time when cells of the cortical plate are just being generated at the ventricular zone. In this case, the labeling pattern at the occipital pole was not bistratified. Rather, labeled cells were situated within a single zone extending from the pial surface inward to the border of the ventricular zone. This finding indicates that the cells of the subplate and marginal zones are generated as a contiguous population that is subsequently split apart by the insertion of cells forming the cortical plate. A comparison between the number of early generated cells found in fetal and newborn brains with that found in adult brains suggests that these cells are generated initially in substantial numbers but then largely disappear during early postnatal life, since injections of [3H]thymidine between E24 and E30 yielded large numbers of labeled cells in the white matter and layer 1 at birth, but very few at 2 months postnatal. This significant loss contrasted with the results from injections made just a few days later (E33) that resulted in large numbers of labeled cells in cortical layer 6 not only at birth but also in adulthood.(ABSTRACT TRUNCATED AT 400 WORDS)

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Prenatal development of functional connections in the cat's retinogeniculate pathway.

The development of functional connections between the axons of retinal ganglion cells and the neurons of the dorsal lateral geniculate nucleus (LGNd) of fetal and neonatal cats was studied using an in vitro assay. Extracellular microelectrode recordings of single units were made from histologically identified sites in the LGNd of isolated diencephalon preparations between embryonic day 39 ( E39 ) and postnatal day 2 (P2). (Gestation is 65 days in the cat.) Postsynaptic units activated by electrical stimulation of one or both optic nerves were found at all ages tested from E39 onwards. Over 90% of the units studied in the fetal preparations received convergent excitation from both optic nerves, compared with roughly half of the units studied in the neonatal optic nerves, compared with roughly half of the units studied in the neonatal preparations. Inhibition was detected in the LGNd of the neonatal preparations, but in only the oldest of the fetal preparations ( E59 ). This physiological change from predominantly convergent excitation to an adult-like mixture of excitation and inhibition seen at birth coincides with the change from mixed to segregated afferent input from the two eyes seen anatomically ( Shatz , C. J. (1983) J. Neurosci . 3: 482-499). These results indicate that attainment of the adult pattern of retinogeniculate connectivity involves the elimination of already functional synapses.

Animals↗

The prenatal development of the cat's retinogeniculate pathway.

The prenatal development of connections between the retina and the lateral geniculate nucleus (LGN) was studied by means of the anterograde axonal transport of 3H-amino acids or horseradish peroxidase injected intraocularly in fetal cats older than embryonic day 27 (E27) and in newborn cats. (Gestation is 65 days.) A retinothalamic pathway exists as early as E28, when label can be seen in both ipsilateral and contralateral optic tracts. Afferents from the contralateral eye are the first to invade the anlage of the LGN by E32 with those from the ipsilateral eye following about 3 days later. Initially, the pattern of labeling within the nucleus is uniform, suggesting that the two sets of afferents must share a good deal of territory at early ages. By E47, however, gaps appear in the labeling pattern contralaterally, indicating that afferents from the two eyes are beginning to segregate from each other. Segregation continues so that by E54 it is possible to identify unambiguously regions of the LGN destined to comprise ipsilateral and contralateral eye layers. By birth, afferent input appears adult-like in organization, with the two sets of afferents almost completely segregated from each other into their appropriate layers. Cellular lamination of the nucleus has just commenced, however, thereby lagging the onset of afferent segregation by about 2 weeks. Prenatal development could be followed much more easily in the horizontal than in the coronal plane of section due to the finding here that the LGN is displaced approximately 90 degrees in the horizontal plane between E40 and E60. Measurements of the area occupied by the ipsilateral and contralateral afferents within the LGN indicated that even prior to segregation, the two sets of afferents are not completely intermixed within the LGN. On the contrary, those from the contralateral eye retain almost exclusive control of some territory throughout development. This detail contrasts with development in primates, in which intermixing of afferents from the two eyes is thought to be complete early on (Rakic, P. (1976) Nature 261: 467-471). Nevertheless, in the cat, as in other mammals, development of the retinogeniculate pathway is broadly characterized by an initial period of overlap followed by a period of segregation that gives rise to the adult pattern of afferent input.

Amino Acids↗

The genesis of efferent connections from the visual cortex of the fetal rhesus monkey.

The prenatal development of the cortical projections to the dorsal lateral geniculate nucleus (LGN), superior colliculus (SC) and pulvinar was studied by autoradiography of orthogradely transported 3H-proline injected into the occipital cortex of fetal rhesus monkeys aged from embryonic day 63 (E63) to E95. Differentiation of pyramidal neurons situated in the infragranular strata of the cortical plate (prospective layers 5 and 6, which give rise to these efferent projections) was also examined in Golgi preparations prepared from specimens of corresponding embryonic ages. In autoradiographs of the E63 fetus, no radioactive label was seen in subcortical structures. In two specimens injected around E70, label was present in the prospective magnocellular layers of the LGN and within the immediately surrounding cell-poor zones. At these young fetal ages, the presence of topographic order in the corticogeniculate projection could not be determined due to the large size of the injection sites relative to the small cerebral vesicles. By E84 the portion of the prospective parvocellular layers adjacent to the white matter also contained label which was characteristically wedge-shaped and appropriately located with respect to the site of the cortical injection, suggesting that topographic order is established. In the oldest fetus (E95) label in the LGN assumed a configuration similar to that seen in the adult. The cortical projection also invades the SC and pulvinar around E70. In the SC, label was initially confined to the stratum opticum, but by E84 it extended into the superficial gray. Thus, all known classes of efferent pathways from the visual cortex to subcortical structures are present by the middle of the 165-day gestational period in rhesus monkey. The one-month period, E63-E97, during which these efferent visual connections are established is characterized by the considerable growth and increased complexity of the dendritic arborization of pyramidal cells in the infragranular cortical layers of area 17. Thus the development of visual cortical efferents occurs in rough synchrony with the genesis of the afferent pathway from the LGN (Rakic, '76a; '79) and with the onset of morphological differentiation of pyramidal neurons in the infragranular cortical layers.

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Siamese cat: altered connections of visual cortex.

In siamese cats, each side of the brain receives a retinal input serving part of the ipsilateral visual field as well as the normal contralateral field representation. Both corticothalamic and cortico-cortical projections are systematically rearranged, but while one is retinotopically appropriate, the other fails to make a distinction between ipsilateral and contralateral fields. Different rules appear to govern the development of these two sets of connections.

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