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W M Cowan

Publications and source records attributed to W M Cowan.

At least 91 records · Page 5Linked to original sources
PubMed1978

An autoradiographic study of the commissural and ipsilateral hippocampo-dentate projections in the adult rat.

The distribution of the associational and commissural afferents to the inner one-fourth of the molecular layer of the dentate gyrus of the rat, has been studied autoradiographically following small injections of 3H-proline into the hilar region of the dentate (from which both groups of afferents arise). Different patterns of axonal labeling are observed after injections into the temporal (i.e., caudal), middle, or septal (rostral) thirds of the hippocampus. Thus after temporal injections labeled commissural and associational afferents are found only in the caudal third of the dentate gyrus, and the grain densities observed on the two sides are markedly asymmetrical around the short, or transverse, axis of the dentate. On the other hand, injections into the middle third of the hippocampus lead to extensive labeling of the commissural and associational afferents throughout the rostral two-thirds of the dentate gyrus, and their distribution, as judged by grain density estimates, is symmetrical on the two sides. Septal injections label fibers over the rostral half of the dentate, and again the labeling pattern on the two sides is asymmetrical (but in the reverse pattern from that seen after temporal injections). These distinctive patterns in the distribution of the two classes of afferents can generally be accounted for on the following assumptions: (1) the commissural and associational afferents share a common cytochemical specificity; (2) they compete with each other for the limited number of synaptic sites available upon the proximal portions of the granule cells: (3) the granule cells are generated along two distinct morphogenetic gradients:from the temporal to the septal pole of the dentate gyrus, and from the tip of its dorsal (or external) to the tip of its ventral (internal) blade; and (4) the first fibers to arrive monopolize the majority of the available synaptic sites, and those that reach their target field later, synapse predominantly upon the last-formed granule cell dendrites. To this extent our findings are consonant with the "temporal hypothesis" first formulated by Gottlieb and Cowan ('72). However, to account for the restricted distribution of afferents from the temporal part of the hippocampus, it is necessary to further postulate that there is some degree of topographic (or region-to-region) specificity in the ipsilateral and contralateral hippocampo-dentate projections.

Animals↗
PubMed1977

An autoradiographic study of the development of the entorhinal and commissural afferents to the dentate gyrus of the rat.

The development of the entorhinal, ipsilateral associational, and commissural afferents to the dentate gyrus have been studied autoradiographically, following the injection of small amounts of tritiated proline into the medial and lateral parts of the entorhinal cortex, and into fields CA3c and CA4 of the hippocampus, in a series of rats, on the third, sixth, and twelfth postnatal days. Clear labeling of the entorhinal afferents were found at the third postnatal day, and from the earliest stage studied the afferents from the two parts of the entorhinal cortex appear to be spatially segregated within the stratum moleculare of the dentate gyrus: the fibers from the lateral entorhinal area occupying the outermost one-third, or so, of this stratum, while those from the medial entorhinal cortex occupy its middle zone. The ipsilateral hippocampo-dentate associational pathway is present at the third postnatal day, but the commissural projection (which shares with it the inner part of the stratum moleculare) could not be labeled until the sixth postnatal day. By the twelfth day the characteristic adult pattern of distribution of the terminals of the two hippocampo-dentate pathways is established. Although this pattern is best accounted for on the basis of a temporal competition for the available synaptic sites on the proximal parts of the dendrites of the granule cells, the spatial segregation of these two fiber systems from those arising in the entorhinal cortex, is probably due to the selective fasciculation of fibers in each group of afferents and to their early cytochemical specificity.

Afferent Pathways↗
PubMed1977

Rat hippocampal neurons in dispersed cell culture.

An in vitro system has been developed for the study of isolated hippocampal neurons from 18- or 19-day rat fetuses. Following trypsinization the cells are plated out at low density on polylysine-treated coverslips in an enriched medium. The isolated neurons rapidly attach to the substrate and initiate process extension. Little reaggregation occurs and the number of non-neuronal cells present is minimal. Unless co-cultured with tissue explants the neurons survive for only a few days; in the presence of hippocampal explants the initial growth of the isolated cells is improved and their survival in culture is extended to about two weeks. Some of the cells in such cultures develop a characteristic branching pattern closely resembling that of maturing hippocampal pyramidal cells in vivo. There is a clear relationship between the stage of the cells' development and their growth in culture. Cells which had completed DNA synthesis about 48 h before dissociation, and which were in the process of migration to the cortical plate, survived best in our cultures. Early post-mitotic cells which were still within the ventricular zone and cells which had already reached the cortical plate grew poorly. This system should permit the study not only of process formation by these cells, but also of their capacity to form specific synapses in vitro and of the biochemical constituents of their surfaces.

Animals↗
PubMed1977

An autoradiographic study of the organization of the efferent connections of the hippocampal formation in the rat.

The efferent connections of the hippocampal formation of the rat have been re-examined autoradiographically following the injection of small quantities of 3H-amino acids (usually 3H-proline) into different parts of Ammon's horn and the adjoining structures. The findings indicate quite clearly that each component of the hippocampal formation has a distinctive pattern of efferent connections and that each component of the fornix system arises from a specific subdivision of the hippocampus or the adjoining cortical fields. Thus, the precommissural fornix has been found to originate solely in fields CA1-3 of the hippocampus proper and from the subiculum; the projection to the anterior nuclear complex of the thalamus arises more posteriorly in the pre- and/or parasubiculum and the postsubicular area; the projection to the mammillary complex which comprises a major part of the descending columns of the fornix has its origin in the dorsal subiculum and the pre- and/or parasubiculum; and finally, the medial cortico-hypothalamic tract arises from the ventral subiculum. The lateral septal nuclei (and the adjoining parts of the posterior septal complex) constitute the only subcortical projection field of the pyramidal cells in fields CA1-3 of Ammon's horn. There is a rostral extension of the pre-commissural fornix to the bed nucleus of the stria terminalis, the nucleus accumbens, the medial and posterior parts of the anterior olfactory nucleus, the taenia tecta, and the infralimbic area, which appears to arise from the temporal part of field CA1 or the adjacent part of the ventral subiculum. The projection of Ammon's horn upon the lateral septal complex shows a high degree of topographic organization (such that different parts of fields CA1 and CA3 project in an ordered manner to different zones within the lateral septal nucleus). The septal projection of "CA2" and field CA3 is bilateral, while that of field CA1 is strictly unilateral. In addition to its subcortical projections, the hippocampus has been found to give rise to a surprisingly extensive series of intracortical association connections. For example, all parts of fields CA1, CA2 and CA3 project to the subiculum, and at least some parts of these fields send fibers to the pre- and parasubiculum, and to the entorhinal perirhinal, retrosplenial and cingulate areas. From the region of the pre- and parasubiculum there is a projection to the entorhinal cortex and the parasubiculum of both sides. That part of the postsubiculum (= dorsal part of the presubiculum) which we have examined has been found to project to the cingulate and retrosplenial areas ipsilaterally, and to the entorhinal cortex and parasubiculum bilaterally.

Animals↗
PubMed1976

The efferent connections of the ventromedial nucleus of the hypothalamus of the rat.

The efferent connections of the ventromedial nucleus of the hypothalamus (VMH) of the rat have been examined using the autoradiographic method. Following injections of small amounts (0.4-2.0 muCi) of tritium labeled amino acids, fibers from the VMH can be traced forward through the periventricular region, the medial hypothalamus and the medial forebrain bundle to the preoptic and thalamic periventricular nuclei, to the medial and lateral preoptic areas, to the bed nucleus of the stria terminalis and to the ventral part of the lateral septum. Some labeled axons continue through the bed nucleus of the stria terminalis into the stria itself, and hence to the amygdala, where they join other fibers which follow a ventral amygdalopetal route from the lateral hypothalamic area and ventral supraoptic commissure. These fibers terminate in the dorsal part of the medial amygdaloid nucleus and in the capsule of the central nucleus. A lesser number of rostrally directed fibers from the VMH crosses the midline in the ventral supraoptic commissure and contributes a sparse projection to the contralateral amygdala. Descending fibers from the VMH take three routes: (i) through the medial hypothalamus and medial forebrain bundle; (ii) through the periventricular region; and (iii) bilaterally through the ventral supraoptic commissure. These three pathways are interconnected by labeled fibers so that it is not possible to precisely identify their respective terminations. However, the periventricular fibers seem to project primarily to the posterior hypothalamic area and central gray, as far caudally as the anterior pole of the locus coeruleus, while the medial hypothalamic and medial forebrain bundle fibers apparently terminate mainly in the capsule of the mammillary complex, in the supramammillary nucleus and in the ventral tegmental area. The ventral supraoptic commissure fibers leave the hypothalamus closely applied to the medial edges of the two optic tracts. After giving off their contributions to the amygdala, they continue caudally until they cross the dorsal edge of the cerebral peduncle to enter the zona incerta. Some fibers probably terminate here, but others continue caudally to end in the dentral tegmental fields, and particularly in the peripeduncular nucleus. Within the hypothalamus, the VMH appears to project extensively to the surrounding nuclei. However, we have not been able to find evidence for a projection from the VMH to the median eminence. Isotope injections which differentially label the dorsomedial or the ventrolateral parts of the VMH have shown that most of the long connections (to the septum, amygdala, central tegmental fields and locus coeruleus) originate in the ventrolateral VMH, and there is also some evidence for a topographic organization within the projections of this subdivision of the nucleus.

Animals↗
PubMed1976

The time of origin and the pattern of survival of neurons in the isthmo-optic nucleus of the chick.

The time of origin of the cells in the isthmo-optic nucleus (ION--the nucleus of origin of centrifugal fibers to the avian retina) has been determined in the chick by a variant of the cumulative labeling method, using 3H-thymidine autoradiography. All the neurons of the ION are generated (i.e., pass through their last phase of DNA synthesis) over a 50-hour period between the latter part of the fifth and the seventh days of incubation (stages 28--31 of the Hamburger and Hamilton ['51] series) but the cells come to be assembled within the nucleus along a distinct temporo-spatial gradient. The earliest-formed cells occupy the ventrolateral part of the nucleus while the last neurons to be generated come to lie along its dorsomedial margin. When the nucleus is numerically complete, around the eleventh day of incubation, it contains about 22,000 neurons, but between the thirteenth and seventeenth days (stages 39 through 43) this number is produced by nearly 60% to about 9,500 cells. Following the radical extirpation of the one optic cup or the circumscribed removal of the neural retina early on the third day of incubation, the cell loss in the contralateral ION is greatly accentuated, so that by the eighteenth day of incubation no cells remain in the nucleus. Serial counts of the numbers of cells in the nucleus on the side of the eye (or retinal) removals show that it, too, undergoes additional cell degeneration, so that by the end of the phase of naturally occurring neuronal loss, only about half the normal number of cells persist in these experimental animals.

Age Factors↗
PubMed1976

The development of the isthmo-optic tract in the chick, with special reference to the occurrence and correction of developmental errors in the location and connections of isthmo-optic neurons.

The development of the centrifugal projection to the chick retina in the isthmo-optic tract (IOT) has been studied by the retrograde transport of the enzyme marker horseradish peroxidase (HRP) injected into the eye at various times during the incubation period. Some neurons in the isthmo-optic nucleus (ION--the cells of origin of the IOT) can first be labeled from the eye following injections on the tenth day of incubation; after injections on the twelfth day or later, about 95% of the neurons can be so labeled. It follows from this that the axons of virtually all the neurons in the ION (including the 60% which normally degenerate between the thirteenth and seventeenth days of incubation) reach the contralateral eye. Since in 12-day old embryos the IOT is between six and seven millimeters in length and HRP can be identified in the perikarya of ION neurons within three and one-half hours, the rate of retrograde transport in the system must be of the order of 48 mm/day. A similar time is required for HRP to appear in the perikarya of ION neurons in post-hatched chicks in which the length of the IOT is estimated to be about 14 mm. This suggests that at some time during the latter half of the incubation period there is a significant acceleration in the rate of retrograde transport, similar to that found for anterograde axonal transport in the chick and rabbit visual systems.

Animals↗
PubMed1976

The development of the isthmo-optic nucleus.

The nucleus of origin of centrifugal fibers to the retina (the so-called isthmo-optic nucleus - ION) has been used as a model for the study of the major features of neural development, from the period of cell proliferation until after the formation of its afferent and efferent connections. 3H-thymidine autoradiography has established that in the chick cells of the ION are generated (i.e., become post-mitotic) between the middle of the 5th and the end of the 7th days of incubation. The first-formed cells are found in the ventrolateral part of the nucleus, while those that are generated at successively later stages come to occupy progressively more medial and dorsal positions within the nucleus. The anlage of the ION can be identified on the 8th day of incubation, and by the 11th day, when it is numerically complete, it occupies a prominent position in the caudo-dorsal part of the midbrain tegmentum at the level of the IVth nerve nucleus. At this stage the nucleus contains about 22,000 neurons, and shows no signs of cytoarchitectonic differentiation. Between the 13th and 17th days of incubation, about 60% of the neurons in the nucleus degenerate; as a result of this degeneration, the arrival of afferent fibers, and the growth of the cells' processes, the nucleus comes to have its characteristic adult form of a complex, folded, bilaminar sheet, in which each part of the retina is precisely represented. Experiments based on the retrograde transport of horseradish peroxidase (HRP) from the eye indicate that the first centrifugal fibers, in the isthmo-optic tract (IOT), reach the retina on the 10 day of incubation, and by the 12th day all but about 5% of the neurons in the ION can be retrogradely labeled in this way...

Afferent Pathways↗
PubMed1975

Hippocampo-hypothalamic connections: origin in subicular cortex, not ammon's horn.

An autoradiographic study of the subcortical projections of the rat hippocampal formation shows that the efferent fibers of the hippocampus proper (fields CA1-4 OF Ammon's horn) do not project to the hypothalamus but are confined to the precommissural fornix, ending primarily in the septum. The fibers that are distributed by way of the fornix system to the hypothalamus (principally the arcuate-ventromedial region and the mammillary nuclei) and the anterior thalamus arise from the subicular region of the cerebral cortex (that is, the subiculum, presubiculum, and parasubiculum).

Animals↗
PubMed1975

Studies on the development of the chick optic tectum. IV. An autoradiographic study of the development of retino-tectal connections.

The normal pattern of innervation of the optic tectum has been studied autoradiographically in a series of chick embryos which were injected intraocularly with [3-H]proline at intervals between the 6th and 21st days of incubation. From the distribution of the radioactively labeled proteins transported in the rapid phase of axonal flow, it is evident that retinal fibers first enter the tectum late on the 6th day of incubation and then spread across its surface from its rostrolateral aspect to its caudo-dorso-medial pole during the ensuing 6 days. At the 9th day, when the fibers have grown across the surface of the rostral half of the tectum, there is no indication that the terminal portions of the axons have left the stratum opticum to enter the outer layers of the stratum grieseum et fibrosum superficiale. The first suggestion of such an invasion of the stratum grieseum et fibrosum superficiale is found at day 10, when labeled fibers can be seen in this stratum, over a restricted, oval, area near the center of the tectum. Over the course of the next 2 days the region of the stratum grieseum et fibrosum superficiale occupied by retinal fibers expands, more-or-less concentrically, until by day 14 some labeled fibers are seen in the outer part of the stratum, throughout the tectum. Concurrent with the ingrowth of optic nerve fibers the final cytoarchitectonic differentiation of the outer layers of the tectum occurs so that by day 18 the autoradiographs show a pattern of labeling of layers a-f of the stratum griseum et fibrosum superficiale similar to that seen in mature, post-hatched chicks. Since the region of the tectum which is first innervated by retinal fibers corresponds to the projection field of the region around the upper end of the choroid fissure where the first ganglion cells are generated, it would appear that the axons of the first-formed ganglion cells grow over the rostral surface of the tectum before establishing the first retino-tectal synapses near the central portion of the tectum. Subsequently, as the ganglion cell population grows concentrically from around the area centralis, there is a parallel expansion of the region in which retino-tectal synapses are being formed in the tectum.

Animals↗