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W M Cowan

Publications and source records attributed to W M Cowan.

At least 73 records · Page 4Linked to original sources
PubMed1980

A quantitative EM autoradiographic study of the commissural and associational connections of the dentate gyrus in the rat.

The distribution of anterogradely transported radioactivity in the ipsilateral associational and commissural afferents to the dentate gyrus, after injections of 3H-proline into the hilar region, has been analyzed in light and electron microscopic autoradiographs of adjoining semi-thin and ultra-thin sections, respectively. In the inner third of the molecular layer, in which the two classes of afferents terminate, between 57% and 69% of the label was found over fine preterminal axons and presynaptic profiles; the remaining radioactivity was about equally distributed between dendritic profiles and other tissue components (mainly glial processes). Estimates of the relative numbers of grains within the peak region of labeling over the molecular layer of the supra- and infrapyramidal blades in the LM and EM autoradiographs (what we have termed the supra:infrapyramidal ratio) are surprisingly close despite appreciable differences in the absolute number of grains in different experiments. This suggests that in selected systems grain density estimates of this type can provide an accurate indication of the relative number of axons and axon terminals derived from the labeled projection systems, at least if the analyses are carried out on the same autoradiographs. Our results provide evidence for the assumption underlying the so-called temporal competition hypothesis (Gottlieb and Cowan 1972) and the report of a re-organization that occurs in the distribution of the associational afferents after hippocampal commissurotomy (O'Leary et al. 1980).

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PubMed1980

Evidence for the sprouting of the associational fibers to the dentate gyrus following removal of the commissural afferents in adult rats.

Following chronic removal of the commissural afferents to the dentate gyrus in adult rats, there is a reorganization of the associational afferents (which are normally co-extensive in their distribution with the commissural fibers) in the inner third of the molecular layer. This has been demonstrated by injecting small amounts of 3H-proline into the hilar region of the dentate gyrus at about the middle of its septotemporal extent (so as to label the cells that give rise to the associational afferents) in normal 24 to 28 week-old rats, and in animals of the same age in which the contralateral hippocampus had been destroyed some 12 to 16 weeks previously. In autoradiographs of the control brains the ratio of the number of silver grains seen over the suprapyramidal blade to that found over the infrapyramidal blade is close to 2:1. Following removal of the commissural input to the dentate gyrus the corresponding ratio is 1:1. Since there is now good evidence to indicate that grain density ratios of this kind accurately reflect the relative numbers of synapses formed by the associational fibers in the two blades, these observaztions make it clear that even in adult animals the associational fibers are capable of reactive synaptogenesis in response to the removal of the commissural afferents.

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PubMed1979

Further observations on hippocampal neurons in dispersed cell culture.

The growth of the processes of dissociated hippocampal neurons from 18- to 20-day-old rat fetuses has been studied in vitro using a method that permits cells to be maintained at relatively low plating densities for periods up to three weeks (Banker and Cowan, '77). Most of the cells are spherical or ovoid when they first attach to the substratum (either polylysine or collagen) but within 24 to 48 hours they begin to put out processes, and by the end of the first week in culture a significant proportion (approximately 45%) come to resemble normal pyramidal cells with a more-or-less triangular shaped soma, a single dominant dendrite-like process emerging from the apex of the soma, and several "basal dendrites" arising from the opposite pole of the cell. Comparisons of the lengths of these dendrite-like processes with those of hippocampal cells in the brains of animals sacrificed on the fourth post-natal day and impregnated by a variant of the Golgi-Cox method, indicate that in some cases the rate of process formation in vitro approximates that in vivo and that the general form of the neurons is remarkably like that of immature pyramidal cells. After a week in culture a second type of process can be recognized. These tend to be finer than those we have identified as dendrites; they are relatively uniform in diameter, frequently give off branches at right angles, and in the electron microscope can be seen to form synapses upon the larger processes and cell somata. These axon-like processes differ from the axons of normal pyramidal cells in two important respects: (i) most commonly they arise from one of the dendritic processes, including, on occasion, the putative "apical" dendrites, and only rarely from the base of the perikaryon; (ii) there may be two or more such processes from a single cell. The thicker, tapering processes can be shown (after incubation in 3H-uridine) to contain large amounts of RNA; newly-synthesized RNA does not extend into the finer, axon-like processes.

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PubMed1979

The connections of the septal region in the rat.

The efferent, afferent and intrinsic connections of the septal region have been analyzed in the rat with the autoradiographic method. The lateral septal nucleus, which can be divided into dorsal, intermediate and ventral parts, receives its major input from the hippocampal formation and projects to the medial septal-diagonal band complex. The ventral part of the nucleus also sends fibers through the medial forebrain bundle to the medial preoptic and anterior hypothalamic areas, to the lateral hypothalamic area and the dorsomedial nucleus, to the mammillary body (including the supramammillary region), and to the ventral tegmental area. The medial septal nucleus/diagonal band complex projects back to the hippocampal formation by way of the dorsal fornix, fimbria, and possibly the cingulum. Both nuclei also project through the medial forebrain bundle to the medial and lateral preoptic areas, to the lateral hypothalamic area, and to the mammillary complex. The medial septal nucleus also sends fibers to the midbrain (the ventral tegmental area and raphe nuclei) and to the parataenial nucleus of the thalamus, while the nucleus of the diagonal band has an additional projection to the anterior limbic area. Ascending inputs to the medial septal nucleus/diagonal band complex arise in several hypothalamic nuclei and in the brainstem aminergic cell groups. The posterior septal nuclei (the septofimbrial and triangular nuclei) receive their major input from the hippocampal formation, and project in a topographically ordered manner upon the habenular nuclei and the interpeduncular nuclear complex. The bed nucleus of the stria terminalis receives its major input from the amygdala (Krettek and Price, '78); but other afferents arise from the ventral subiculum, the ventromedial nucleus, and the brainstem aminergic cell groups. The principal output of the bed nucleus is through the medial forebrain bundle to the substantia innominata, the nucleus accumbens, most parts of the hypothalamus and the preoptic area, the central tegmental fields of the midbrain, the ventral tegmental area, the dorsal and median nuclei of the raphe, and the locus coeruleus. The bed nucleus also projects to the anterior nuclei of the thalamus, the parataenial and paraventricular nuclei, and the medial habenular nucleus, and through the stria terminalis to the medial and central nuclei of the amygdala, and to the amygdalo-hippocampal transition area.

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PubMed1979

Evidence for an input to the molecular layer and the stratum granulosum of the dentate gyrus from the supramammillary region of the hypothalamus.

Injections of a mixture of tritiated amino acids were made into the posterior hypothalamus in a series of rats and cats. In every case in which the injection involved a significant proportion of the cells in the supramammillary region, labeled fibers could be followed to the dentate gyrus, the anterior hippocampal rudiment and the induseum griseum of both sides. In the dentate gyrus the hypothalamic afferents terminate in a narrow band in the outer half of the stratum gramulosum and the inner 20 micron or so, of the stratum moleculare, immediately deep to the zone of termination of the associational and commissural afferents. As judged by silver grain counts across the width of the zone of labeled terminals, the projection to the ipsilateral side is several times as heavy as that to the contralateral side, and although it involves the entire septo-temporal (=rostro-caudal) extent of the gyrus on both sides, the projection to the suprapyramidal (inner) blade of the dentate gyrus is approximately twice as heavy as that to the infrapyramidal (outer) blade.

Amino Acids↗
PubMed1979

The morphology of the hippocampus and dentate gyrus in normal and reeler mice.

The morphology of the hippocampus and dentate gyrus in normal and reeler mice has been studied in Nissl, myelin, Golgi, Timm's sulfide silver and gold chloride-sublimate preparations. It is evident from both cell-and fiber-stained sections that despite the obvious defect in the positioning of the hippocampal pyramidal and dentate granule cells in the reeler mouse within the radial dimension, the hippocampal formation as a whole shows a normal and consistent progression of cytoarchitectonic fields along its transverse axis, and a normal and consistent progression of changes in the structure of the hippocampus and dentate gyrus along their longitudinal axes. Thus, at least in these structures, the reeler gene seems to exert its effect only in the radial dimension. Cell counts in the area dentata indicate that the number of dentate granule cells in the reeler mouse is reduced compared to that found in normal or heterozygous animals. Although it has been known for some time that the number of granule cells in the reeler cerebellar cortex is markedly reduced, this appears to be the first evidence for a reduction in cell number in a forebrain structure. All the major cell types normally found in the hippocampus and the dentate gyrus are recognizable in Golgi-stained preparations from the brains of reeler mutants. However, in both regions there are a number of abnormalities in the appearance of the cells which seem to be related to the cellular ectopia. Thus, whereas most of the pyramidal and granule cells which attain a normal position in the mutant usually have normal, or near-normal dendritic arbors, the dendrites of nearly all ectopic cells are severely distorted, both in their orientation and general configuration. In preparations stained by the Timm's sulfide silver technique it is evident that the general lamination pattern seen in normal mice is retained in the reeler hippocampus and dentate gyrus despite the gross malpositioning of many of the relevant neurons. However, although the overall laminar arrangement is preserved, there are some fairly consistent abnormalities; for example, the normal trilaminar staining pattern seen in the stratum moleculare of the dentate gyrus is replaced in the reeler by a bilaminar pattern. In gold chloride-sublimate impregnated preparations there is no obvious alignment of the astrocytes in the stratum moleculare of the dentate gyrus in either normal or reeler mice. Moreover, the distribution of the astrocytes within this zone is fairly normal in the reeler mouse, although, in general, these cells appear to be more consistently stellate in form than in normal animals.

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PubMed1979

The development of the hippocampus and dentate gyrus in normal and reeler mice.

The histogenesis, the time of origin and the pattern of migration of the cells in the hippocampus and dentate gyrus, have been studied in normal and reeler mice. The earliest indication of a defect in the reeler hippocampus is seen on the fifteenth embryonic day (E15) which is at least 24 hours after the first indication of a defect in the neocortex. It is not until E18, that the dentate gyrus shows signs of its incipient abnormality. It appears then, that in both the hippocampus and the dentate gyrus the gene defect first manifests itself at the stage at which the definitive cellular layers are assembled. Experiments involving the injection of 3H-thymidine (3H-TdR) at different developmental stages have confirmed that the site and rate of cellular proliferation in the reeler hippocampus and dentate gyrus are normal, as is the initial pattern of cell migration. However, in the reeler dentate gyrus, most postnatal cell proliferation occurs ectopically and in the hippocampus the normal "inside-out" sequence of neurogenesis is reversed, the earliest pyramidal cells generated coming to lie superficially within the stratum pyramidale and the later formed cells being added at progressively deeper levels. There is no discernible gradient in the time of origin of the granule cells in the radial dimension of the reeler dentate gyrus, whereas there is an obvious "outside-in" gradient in the normal animal. The characteristic gradients in cell proliferation seen in the transverse and longitudinal dimensions of the normal dentate gyrus are, however, also evident in the reeler mouse. Taken together, these observations suggest that the reeler gene exerts its effect on neuronal position only in the radial dimension, and does so at a stage of development subsequent to the proliferation and initial migration of the relevant neurons. Timm's sulfide silver preparations indicate that the characteristic staining patterns seen in the dentate gyrus and hippocampus appear at the same time, and mature at the same rate in normal and reeler mice.

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PubMed1979

The organization of certain afferents to the hippocampus and dentate gyrus in normal and reeler mice.

The organization of certain of the major afferents to the hippocampus and dentate gyrus has been studied in normal and reeler mutant mice using the autoradiographic and the anterograde degeneration methods. The distribution of the hippocampal and dentate afferents which arise in the medial and lateral parts of the entorhinal cortex and the hippocampus of both sides, has been found to be generally similar to that previously described in the rat, but there are a few minor differences that are discussed in the text. Despite the marked ectopia of many of the neurons in the hippocampal formation in the reeler mouse, the principal afferents to the hippocampus and the dentate gyrus maintain many of the features seen in normal mice. In particular, they maintain a normal radial sequence and a characteristic laminated and complementary arrangement. However, there are a number of significant differences in their distribution; for example, in the reeler mouse, the entorhinal afferents occupy the entire radial extent of the stratum moleculare of the dentate gyrus, whereas in normal mice they are restricted to the outer four-fifths of this layer. Furthermore, in the mutant the commissural and associational afferents to the dentate gyrus do not occupy the inner one-fifth of the molecular layer (as they do in normal animals) but rather are spread throughout the zone containing granule cells, which includes both the poorly-defined stratum granulosum and most of the hilar region of the dentate gyrus. Some of the developmental and functional implications of these and other abnormalities in the organization of the afferents to the hippocampus and dentate gyrus are discussed.

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PubMed1979

An autoradiographic study of the efferent connections of the lateral hypothalamic area in the rat.

The efferent connections of the lateral hypothalamic area (LHA) have been analyzed in a series of 30 rat brains with injections of 3H-amino acids into different parts of the area and the surrounding regions. Our findings indicate that all parts of the LHA contribute ascending and descending fibers to the medial forebrain bundle, and also project medially to certain of the adjoining hypothalamic nuclei. All levels of the LHA appear to send some fibers to a continuous group of structures that extends from the medial septal-diagonal band complex rostrally, through the lateral preoptic and lateral hypothalamic areas to the mammillary complex and the ventral tegmental area caudally. In addition, it is evident that cells at different levels within the LHA may have differential projections. Thus, the anterior and lateral parts of the LHA also appear to project substantially to the anterior hypothalamic area, the ventromedial and dorsomedial hypothalamic nuclei, the parataenial and paraventricular nuclei of the thalamus, and the medial part of the lateral habenular nucleus. Similarly, cells in the tuberal and posterior parts of the LHA project to the central gray, the longest projections from the posterior region reaching as far caudally as the central tegmental field, the parabrachial nucleus, the locus coeruleus, and the superior central and dorsal nuclei of the raphe. Viewed as a whole, the LHA is therefore well-suited to integrate inputs from the limbic system and brainstem and to relay them on the one hand to the medial zone of the hypothalamus and on the other to virtually every structure closely associated with the medial forebrain bundle and to the nuclei of origin of the major ascending monoaminergic systems.

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PubMed1979

A study of glial cell proliferation in the molecular layer of the dentate gyrus of the rat following interruption of the ventral hippocampal commissure.

The proliferation of glial cells in the molecular layer of the dentate gyrus in response to lesions of the ventral hippocampal commissure, has been studied autoradiographically following intraventricular injections of 3H-thymidine. Within 24 h of commissurotomy there is an appreciable increase in the number of labeled cells throughout the molecular layer which reaches its peak at approximately 36 h. This generalized glial hyperplasia persists for at least 5--6 weeks and there does not appear to be a secondary re-distribution of the newly-generated glial cells as has been reported after entorhinal lesions (Gall et al., 1979). In semi-thin plastic sections most of the proliferating cells more closely resemble the "medium-shade oligodendrocytes" of Ling et al. (1973) than typical microglia; the reactive astrocytes do not appear to participate in the glial proliferation.

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PubMed1978

The efferent connections of the anterior hypothalamic area of the rat, cat and monkey.

The general morphology and topographic relations of the anterior hypothalamic area (AHA) in the rat, cat and squirrel monkey have been described, and its efferent connections analyzed autoradiographically, after small injections of 3H-labeled amino acids into, or around, the area. In all three species the AHA is rather poorly separated from the surrounding preoptic and hypothalamic areas and nuclei but shows three distinct cellular condensations, located rostrally, centrally, and posterodorsally. Closely associated with the AHA are the retrochiasmatic area, the anterior periventricular nucleus and the scattered neurons usually referred to as the accessory supraoptic nucleus. The AHA has primarily short connections to the adjoining medial preoptic area, the lateral hypothalamic area, the periventricular nucleus, the dorsomedial nucleus, and to the "capsule" of the ventromedial nucleus. However, it also has certain more distant projections, rostrally to a narrow zone centered in the ventral part of the lateral septal nucleus, and caudally to the dorsal premammillary nuclei, the posterior hypothalamic area and the central gray. There is some evidence to suggest that the various subdivisions of the AHA have different efferent connections. Thus the posterodorsal cell condensation appears to give rise to the bilateral projection to the dorsal premammillary nuclei, while the projections to the septum, the posterior hypothalamic area and the central gray seem to have their origin in the central condensation. Similarly, the retrochiasmatic area sends its efferents through the ventral supraoptic commissure to the amygdala, the anterior periventricular nucleus contributes to the periventricular fiber system and to the external lamina of the median eminence, and the accessory supraoptic neurons project to the internal lamina of the median eminence.

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