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W M Cowan

Publications and source records attributed to W M Cowan.

At least 37 records · Page 2Linked to original sources
PubMed1986

Topographic targeting errors in the retinocollicular projection and their elimination by selective ganglion cell death.

In adult rats, as in other rodents, the retinocollicular projection is topographically organized in a very precise manner. Experiments involving the use of the retrogradely transported fluorescent dye fast blue as either a short- or long-term marker in neonatal rats indicate that the precision of this retinotopic projection does not arise ab initio, but rather is brought about by the preferential elimination of those ganglion cells whose axons project to topographically inappropriate regions of the colliculus. Such topographic targeting errors have been identified along both the rostrocaudal and mediolateral axes of the colliculus, and their elimination occurs during the period of naturally occurring ganglion cell death, which is completed by about postnatal day 10. When impulse activity in the retinal ganglion cell axons is blocked by repeated intraocular injections of the sodium channel-blocking agent tetrodotoxin (TTX) throughout the postnatal period of ganglion cell death, the preferential loss of the incorrectly projecting ganglion cells does not occur in the activity-blocked eye, although, as reported elsewhere, the overall loss of ganglion cells is comparable to that seen in normal animals. This supports the notion that the mechanism for selecting against incorrectly projecting ganglion cells is based on impulse activity among the competing ganglion cell axons. However, under activity-block conditions, the aberrantly projecting axons appear to retract from the caudal margin of the colliculus. The death of retinal ganglion cells during development thus seems to serve 2 purposes: It provides for the quantitative matching of the ganglion cell population to the needs of its central projection fields, and, at the same time, it serves to selectively eliminate those cells whose axons project to inappropriate targets or to inappropriate regions within the correct target fields.

Amidines↗
PubMed1985

The thalamic relations of the caudal inferior parietal lobule and the lateral prefrontal cortex in monkeys: divergent cortical projections from cell clusters in the medial pulvinar nucleus.

The thalamic relations of the caudal inferior parietal lobule and the dorsolateral prefrontal cortex in monkeys have been investigated with both anterograde and retrograde neuroanatomical tracing techniques. The results of these experiments indicate that the medial pulvinar nucleus (Pul.m.) is the principal thalamic relay to the gyral surface of the caudal inferior parietal lobule (area 7a). Within the Pul.m. there are two or three disklike aggregates of neurons which project to area 7a; these disklike neuronal aggregates are oriented from dorsomedial to ventrolateral and extend over most of the rostrocaudal extent of the nucleus. Within these disks there are rodlike clusters of neurons which are elongated in the rostrocaudal dimension of the thalamus, and which project in a topographically ordered manner to area 7a. Thus, the more rostrally located neurons within the Pul.m. disks project to more rostral parts of area 7a and, conversely, the more caudally located neurons project to the caudal part of this cortical field. Similarly, the medial part of each disk projects to the lateral part of area 7a while the laterally placed neurons project to the medial part of the cortical field. In addition to its input from the Pul.m., area 7a is also reciprocally connected with the magnocellular division of the nucleus ventralis anterior, with the nuclei which abut upon the medullary capsule of the laterodorsal nucleus, and with the suprageniculate nucleus and the nucleus limitans. The cortex on the lateral bank of the intraparietal sulcus (the so-called lateral intraparietal area, LIP) projects principally to the lateral pulvinar nucleus (Pul.l) of the thalamus rather than to Pul.m. Area LIP has been found to project to the pregeniculate nucleus, the zona incerta, the anterior pretectal nucleus, and the superior colliculus. Area 7a projects to none of these structures, but it does project to the posterior pretectal nucleus. The thalamic relations of the neighboring cortical regions, such as the prelunate gyrus and area 7b, are also distinct from those of area 7a. It thus seems that the prelunate gyrus is primarily interconnected with the Pul.l., and area 7b with the oral pulvinar nucleus. Taken together these different subcortical relationships provide further evidence for the view that the caudal inferior parietal lobule is not a homogeneous cortical area, but is composed of a number of subsidiary fields. The projection from the Pul.m. to the lateral prefrontal cortex arises from disklike aggregates of neurons, similar in their orientation to the neuronal disks that project to area 7a.(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗
PubMed1985

On the number of neurons in the dentate gyrus of the rat.

We have estimated the number of dentate granule cells in Sprague-Dawley and Wistar rats at 1, 4 and 12 months of age. In Sprague-Dawley rats the number of granule cells is relatively constant throughout this period at about 1 million. In Wistar rats, on the other hand, there is a progressive increase in the number from about 700,000 at 1 month to 1 million at 4 months; thereafter the number declines to about 800,000 at 1 year. Estimates of the numbers of cells in the polymorphic zone that can be stained immunohistochemically for somatostatin, cholecystokinin, vasoactive-intestinal peptide, and glutamic acid decarboxylase show no appreciable differences in the two strains.

Age Factors↗
PubMed1985

Postnatal development of the ipsilateral retinocollicular projection and the effects of unilateral enucleation in the golden hamster.

Anterograde transport of wheat germ agglutinin conjugated to horseradish peroxidase (WGA-HRP) was used to study the normal development of the ipsilateral retinocollicular projection in golden hamsters, and to examine the effect of enucleation of the other eye at birth. In neonatal animals there were retinal fibers and sparsely distributed granular labeling in the superficial layers of the ipsilateral superior colliculus over its entire areal extent. Differences in the uncrossed projections of normal and enucleated animals first became clear at day 5. In normal animals, retinal fibers withdrew from the superficial layers of the superior colliculus, and the projection became concentrated in the stratum opticum, where denser clumps of label in the rostral part of the superior colliculus were first seen at day 5. In enucleated animals, the retinal projection persisted in the most superficial layers, and the density of labeling was higher than in normals. The very sensitive WGA-HRP technique showed retinal fibers extending to the caudal pole of the superior colliculus at all ages: even in normal animals more than 2 weeks of age some fibers reached as far as the inferior colliculus. When the shrunken size of the superior colliculus in the enucleated animals was taken into account, the total areal distribution of the ipsilateral projection was similar in normal animals and enucleates. The major difference between the two groups was in the higher density of ipsilateral labeling, especially in the caudal part of the superior colliculus, and in its more superficial laminar distribution in the enucleated animals.

Aging↗
PubMed1985

Callosal and prefrontal associational projecting cell populations in area 7A of the macaque monkey: a study using retrogradely transported fluorescent dyes.

The spatial interrelationship of neurons in area 7a in the inferior parietal lobule that project through the corpus callosum to the corresponding field in the contralateral hemisphere or to the ipsilateral prefrontal cortex has been analyzed in macaque monkeys by using double-labeling procedures with retrogradely transported fluorescent dyes. The populations of callosal and associational projecting neurons have similar laminar distributions and are topographically intermingled. Less than 1% of the neurons were double-labeled, thus suggesting that the two populations are largely separate. Two-dimensional reconstructions of the distribution of labeled cells made on flattened reconstructions of the inferior parietal lobule revealed that the areal distribution of the two cortico-cortical output arrays is complex. Although each pattern of labeling showed some discontinuities in density, there was no obvious periodicity within or between the spatial distributions of the two projecting populations. It was consistently observed that the cortex of the lateral wall of the intraparietal sulcus, adjacent to area 7a, projects more heavily to the prefrontal cortex than does area 7a itself.

Animals↗
PubMed1985

Changes in the numbers of optic nerve fibers during late prenatal and postnatal development in the albino rat.

We have estimated from electron micrographs the numbers of axons in the optic nerves of a series of albino rats at 8 different ages ranging from embryonic day (E)18 through postnatal day 28. The number of axons was found to reach a maximum of about 325,000 (324,790 +/- 38,589) on E20, and to decline to about 275,000 (273,744 +/- 20,973) by the day of birth. By the middle of the second postnatal week, the number was further reduced to a stable figure of just over 100,000 (105,809 +/- 7,610). This represents a loss of two-thirds of the axons from the peak value at E20, and suggests that there is a comparable degree of cell death among the retinal ganglion cells. The reduction in the number of optic nerve fibers is not affected significantly by the removal of the opposite eye at birth.

Animals↗
PubMed1985

On the formation of eye dominance stripes and patches in the doubly-innervated optic tectum of the chick.

By surgically dividing the region of the presumptive optic chiasm in chick embryos on the third day of incubation (around stage 15), we have been able to induce substantial numbers of optic nerve fibers to grow aberrantly into the ipsilateral optic tract. As a result, many of the visual centers that are normally innervated only by fibers from the contralateral retina received fibers from both eyes. The proportion of fibers going to each tectal lobe varied from case to case, but in about one-third of the animals the tectal lobes received approximately equal numbers of fibers from each eye. In animals that survived until embryonic days 17-19 (which is beyond the period of retinal ganglion cell death) labeling of the two eyes with WGA-HRP and [3H]proline respectively, revealed a pattern of sharply defined eye dominance stripes or patches in the stratum griseum et fibrosum superficiale (SGFS) of the optic tectum, and in the ventral lateral geniculate nucleus. Less clearly segregated eye dominance zones were seen in the ectomammillary nucleus and the nucleus externus. The size and distribution of the stripes varied depending on the number of fibers projecting from each eye to a given tectal lobe; the minimum size was about 75 micron, while the maximum was large enough to occupy almost the entire tectal lobe. In animals in which the tectal input from the two eyes was roughly equal, the stripes varied in width between 75 micron and about one-third of the surface of the tectal lobe. The orientation of the stripes was consistently orthogonal to the direction of fiber ingrowth from the optic tract. From the earliest stages of optic fiber ingrowth, the fibers from the two eyes are completely intermixed in the stratum opticum (SO). However, on embryonic day 12, shortly after they have begun to penetrate into the SGFS, they are already segregated into stripes, although the stripe borders are very fuzzy. This suggests that the fibers from the two eyes may overlap at this stage. The phase of stripe formation coincides with that of naturally occurring retinal ganglion cell death, and we suggest that the two processes are interlinked.

Animals↗
PubMed1984

Regressive events in neurogenesis.

The development of most regions of the vertebrate nervous system includes a distinct phase of neuronal degeneration during which a substantial proportion of the neurons initially generated die. This degeneration primarily adjusts the magnitude of each neuronal population to the size or functional needs of its projection field, but in the process it seems also to eliminate many neurons whose axons have grown to either the wrong target or an inappropriate region within the target area. In addition, many connections that are initially formed are later eliminated without the death of the parent cell. In most cases such process elimination results in the removal of terminal axonal branches and hence serves as a mechanism to "fine-tune" neuronal wiring. However, there are now also several examples of the large-scale elimination of early-formed pathways as a result of the selective degeneration of long axon collaterals. Thus, far from being relatively minor aspects of neural development, these regressive phenomena are now recognized as playing a major role in determining the form of the mature nervous system.

Aging↗
PubMed1984

An EM autoradiographic study of the hypothalamo-hippocampal projection.

Previous studies have shown that in many different mammals there is a small but distinct projection from the supramammillary region in the caudal hypothalamus to the junctional region between the regio superior and regio inferior of the hippocampus. We have analyzed the mode of termination of this hypothalamo-hippocampal projection in the rat by electron microscopic (EM) autoradiography following injections of [3H]proline into the caudal hypothalamus. The projection is confined to the regio inferior where it is centered over the subicular end of field CA3, but also spans the adjoining region, field CA2. In our material the highest densities of labeling have been seen over the deeper part of the pyramidal cell layer and in the adjacent stratum oriens but, in addition, above background levels of labeling have been found superficial to the pyramidal cell layer in the stratum lucidum and the deeper part of the stratum radiatum. Most of the labeled synapses appear to be on the perikarya and primary dendrites of the hippocampal pyramidal cells, but some axo-spinous contacts have also been seen. All the labeled boutons contained clear, spheroidal synaptic vesicles and made asymmetric, Type I, contacts with their targets.

Animals↗
PubMed1984

The commissural connections of the monkey hippocampal formation.

The commissural connections of the hippocampal formation have been analyzed in the monkey (Macaca fascicularis) using both anterograde and retrograde labeling techniques. We have observed a number of striking differences between the organization of the commissural projections in the monkey and that observed in the rodent brain. In particular, only the rostral (or uncal) part of Ammon's horn (or hippocampus proper) and the associated part of the dentate gyrus have been found to be connected by commissural fibers. This is in marked contrast to the organization of the crossed connections in the rodent brain where both major fields of the hippocampus (i.e., the regio superior and the regio inferior) receive a strong, topographically organized, projection throughout their rostrocaudal extent from the regio inferior of the opposite side, while the inner third of the molecular layer of the entire dentate gyrus receives a topographically organized input from cells in the hilar region of the contralateral dentate gyrus. The subicular complex of the monkey gives rise to a substantially greater number of commissurally directed fibers. The subiculum itself projects to the posterior portion of the contralateral medial entorhinal cortex and receives a less substantial reciprocal projection from this same area; the subiculum does not appear to be homotopically interconnected. The presubiculum gives rise to the major commissural projection of the monkey hippocampal formation. From all rostrocaudal levels of the presubiculum there is a robust projection to the contralateral medial entorhinal cortex. This projection seems to be topographically organized and terminates most heavily in layers III and IV of the entorhinal cortex. This crossed presubiculo-entorhinal projection is paralleled in its organization by an associational projection from the presubiculum to the ipsilateral entorhinal cortex, but interestingly, the presubiculum does not seem to project to the presubiculum of the opposite side. The parasubiculum projects to neither the contralateral entorhinal cortex nor the contralateral parasubiculum. However, the subicular complex as a whole appears to be in receipt of a minor input from the contralateral parahippocampal gyrus (fields TF and TH of Bonin and Bailey). Cells primarily in layer III of the medial entorhinal cortex (area 28a) project homotopically to the contralateral entorhinal cortex where they terminate in layer III. The medial entorhinal cortex also gives rise to a minor projection to the contralateral parasubiculum and to the regio superior of the contralateral hippocampus and the caudalmost part of the outer molecular layer of the dentate gyrus.(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗
PubMed1984

A stereotaxic atlas of the brain of the cynomolgus monkey (Macaca fascicularis).

Outline drawings of representative frontal sections of the Macaca fascicularis brain are presented in stereotaxic coordinates. The levels extend from the rostral tip of the neostriatum to the posterior end of the deep cerebellar nuclei. The illustrations are based on the photographs of unstained frozen sections of three formalin-fixed brains in which stainless steel needles were inserted to mark the horizontal zero and several anteroposterior positions. The sections were not stained in order to prevent shrinkage. Stereotaxic measurements were taken in situ of the highest points on the cortical surface, the position of the central and lunate sulcus, and of certain landmarks at the base of the cranium in a large number of monkeys. These data along with brain dimensions and the weight of animals are displayed in tables to indicate individual variations and to aid investigators in determining the best stereotaxic coordinates for a given structure. It is recommended that the cortical point of entry for an electrode or needle be routinely noted and be compared to the parameters in the atlas to compensate for deviations in the horizontal plane.

Animals↗
PubMed1984

Survival of isthmo-optic neurons after early removal of one eye.

In a series of normal 12- or 13-day-old chick embryos in which the neuroanatomical tracer wheat germ agglutinin conjugated to horseradish peroxidase (WGA-HRP) was injected into one eye, about 25,000 neurons were found to be retrogradely labeled in the isthmic region of the brain. Of these, about 100 were found on the side of the injection, whereas about 22,000 were found in the contralateral isthmo-optic nucleus (ION, the nucleus of origin of centrifugal fibers to the retina) and a further 3000 ectopic cells were present on this side but lay outside the borders of the ION. After comparable injections on the 18th day of incubation or later, no more than 40 retrogradely labeled neurons were seen on the side of the injection, and on the contralateral side the numbers of neurons in the ION and in the ectopic ION population were reduced by about 60% to approximately 9500 and 1500 cells, respectively. In the present study we have re-examined the effects of removing one optic vesicle or optic cup on the survival and distribution of isthmo-optic neurons in two further series of chick embryos: in the first series the animals were injected intraocularly with WGA-HRP on the 12th day of incubation; in the other the eye injections were done on day 18, 19 or 20. In animals in which the eye rudiment was removed on or before stage 13 of the Hamburger and Hamilton series, essentially all of the centrifugally projecting neurons on both sides of the brain could be labeled from the surviving eye at day 12; however, in chicks operated upon after stage 13 the distribution of the labeled ION neurons was indistinguishable from that in a normal 12 day embryo. In monocular chicks that were allowed to survive beyond the period of naturally occurring cell death in the ION (i.e. beyond day 17) a variety of labeling patterns was seen in the ION and the surrounding region. In nearly all of the animals in which the eye was removed after stage 13, the number of labeled neurons on the side contralateral to the surviving eye was comparable to that seen in a normal, unoperated embryo, whereas virtually no cells were labeled in the isthmic region of the opposite (ipsilateral) side.(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗
PubMed1984

Activity and the control of ganglion cell death in the rat retina.

In newborn rats each retina projects principally to the contralateral superior colliculus, but there is also a sparse projection to the whole of the ipsilateral superior colliculus. During the first 2 weeks postnatally the ipsilateral projection normally becomes restricted to the rostromedial part of the superior colliculus. The restriction of this projection is due to the preferential death of ipsilaterally projecting retinal ganglion cells and is apparently the result of competition between optic fibers from the two eyes, since it can be prevented by enucleation of the opposite eye at birth. To determine if electrical activity plays a role in the normal restriction of the ipsilateral retinocollicular projection, the sodium channel-blocking agent tetrodotoxin was administered to one or both eyes during the first 2 weeks postnatally. Tetrodotoxin blockade of activity in one eye resulted in the persistence of a sparse projection from the opposite eye throughout the ipsilateral superior colliculus and the survival of a substantial number of the ipsilaterally projecting retinal ganglion cells in that eye that would normally have died. When both eyes were treated with tetrodotoxin no restriction of the ipsilateral projection was seen on either side. These findings suggest that the competition between retinal ganglion cell axons (either for terminal space or an essential trophic factor), which normally leads to retinal ganglion cell death and the restriction of the ipsilateral retinocollicular projection, is mediated in some way by electrical activity.

Aging↗
PubMed1983

Evidence for a direct projection from the superior temporal gyrus to the entorhinal cortex in the monkey.

During the course of a larger study of the afferent and efferent connections of the entorhinal cortex in the macaque monkey we have found evidence for a hitherto undescribed projection to the entorhinal cortex from the superior temporal gyrus. The evidence is derived principally from experiments in which small volumes of wheat germ agglutinin-conjugated horseradish peroxidase (WGA-HRP) were injected into different parts of the entorhinal cortex, but has been confirmed by 3H-amino acid autoradiography. After WGA-HRP injections into the entorhinal cortex, retrogradely labeled neurons have been seen mainly in layer III, but also to some extent in layer VI, throughout much of the superior temporal gyrus. The projection appears to be topographically organized in the sense that the ventral insular cortex and the adjoining temporal operculum have been found to project to the periamygdaloid cortex and the lateral division of the entorhinal cortex; the convexity of the superior temporal gyrus and the cortex along the dorsal bank of the superior temporal gyrus project further caudally to the medial division of the entorhinal cortex; and the cortex surrounding the fundus of the superior temporal sulcus projects to the perirhinal cortex. Following an injection of 3H-amino acids into the convexity of the superior temporal gyrus, terminal labeling has been seen over layers I and II of the entorhinal cortex and over layer I in the most lateral portion of the presubiculum. While the distribution of retrogradely labeled cells in our WGA-HRP experiments encompasses several cytoarchitectonically distinguishable areas in the superior temporal gyrus, the most heavily labeled field appears to coincide with what Gross and his colleagues have termed the 'superior temporal polysensory area' on the dorsal bank of the superior temporal sulcus.

Afferent Pathways↗
PubMed1983

The development and restriction of the ipsilateral retinofugal projection in the chick.

Although it is generally believed that the central projections of the retina in birds are entirely crossed, using wheat germ agglutinin-conjugated horseradish peroxidase (WGA-HRP) as an anterograde tracer, we have found that in normal posthatched chicks there is a small ipsilateral retinofugal projection to the diencephalon and midbrain. Most of the ipsilateral fibers appear to be directed to the lateral anterior and dorsolateral anterior nuclei of the thalamus, to the pretectal region, and to the ectomammillary nucleus and the adjoining nucleus externus. Even in the best preparations the numbers of ipsilateral fibers are so small that it is hardly surprising that they have been overlooked in previous axonal degeneration and autoradiographic experiments. A significantly larger ipsilateral retinal projection develops during the second week of incubation. The ipsilaterally directed fibers can be first seen on the fifth day of incubation and their numbers appear to increase until about embryonic day 12. At this stage the projection involves substantially more fibers than at hatching and is also more extensive in its distribution; in fact, in its general organization (but not its size) it closely parallels the normal crossed retinofugal system, contributing fibers to essentially all the primary visual relay nuclei in the diencephalon and midbrain and to much of the optic tectum, where the densest projection is to its caudomedial aspect. During the second week of incubation there is also a small number of retinal fibers, which after crossing in the optic chiasm, recross the midline in the posterior and tectal commissures (and also in the tectal roof plate), before ending in the pretectal region of the ipsilateral side. In addition, there is a markedly aberrant projection from the retina into the contralateral optic nerve. Most of the ipsilateral retinal fibers are eliminated between the twelfth and sixteenth days of incubation, and by day 17 the ipsilateral projection is reduced to its mature form. The progressive reduction in the ipsilateral projection occurs at a time when it is known (from other studies) that there is an appreciable loss of retinal ganglion cells; but whether the reduction is due to neuronal death or to the selective elimination of ipsilateral axon collaterals remains to be determined. The existence of a significant ipsilateral retinofugal component early in development, probably accounts, in part, for the distinctive and persistent ipsilateral projection that occurs if one eye is removed during the first few days of incubation.

Animals↗
PubMed1983

Immunohistochemical localization of monoclonal antibodies to the nicotinic acetylcholine receptor in chick midbrain.

We used the indirect immunofluorescence method to determine the crossreactivity of a library of 57 monoclonal antibodies (mAbs) against each of the subunits of the nicotinic acetylcholine receptor (nAcChoR) isolated from Torpedo and Electrophorus electric organs or from fetal calf and human muscle, with specific neural elements in the midbrain of the chick. Out of 17 mAbs that recognized motor end plates on chick muscle, 14 produced a similar pattern of labeling in the midbrain: the neuronal perikarya and dendrites in the lateral spiriform nucleus (SpL) were intensely labeled, and there was moderate labeling of fibers in certain of the deeper layers of the optic tectum, which disappeared after the SpL was destroyed electrolytically. Two lines of evidence suggest that the mAbs may be crossreacting with nAcChoRs in the midbrain. First, all of the mAbs that stained the SpL also stained neuromuscular junctions in skeletal muscle, whereas none of the 40 mAbs that failed to stain end plates crossreacted with the SpL; second, in vitro immunological studies and blocking experiments on tissue sections (in which unlabeled mAbs were used to block the staining of a directly fluorescein-treated mAb) indicated the presence of mAbs specific for unique antigenic determinants on all four of the subunits (alpha, beta, gamma, and delta) from Torpedo nAcChoR in chick midbrain and muscle. On the other hand, the distribution of mAb staining in the optic tectum does not closely parallel that of either acetylcholinesterase staining or of 125I-labeled alpha-bungarotoxin binding; no toxin binding has been observed autoradiographically in the SpL, but the nucleus does contain moderately dense acetylcholinesterase staining. Take together, our observations suggest that there may be a cholinergic input to the SpL and that the projection fibers from the SpL to the optic tectum (which are also stained with an antiserum to [Leu]enkephalin) may contain presynaptic nAcChoRs. It is clear, however, that the distribution of the putative nAcChoRs, alpha-bungarotoxin binding sites, and acetylcholinesterase staining in the avian midbrain are quite different, although they do overlap to some degree in the deeper layers of the optic tectum.

Acetylcholinesterase↗
PubMed1983

Topographic organization of certain tectal afferent and efferent connections can develop normally in the absence of retinal input.

To test the hypothesis that the topographic organization of the connections of the optic tectum is determined during development by the "retinotopically" ordered input that it receives from the eye, we have mapped certain of the connections of the tectum in chicken embryos and chicks in which both eye rudiments were removed before the outgrowth of optic fibers. Because several of the connections of the tectum are normally organized retinotopically, we should expect, if this hypothesis were correct, that some or all of these connectional patterns would be significantly altered in such "eyeless" chickens. In fact, we have found that the connections formed between the optic tectum and two of the isthmic nuclei, with which it is reciprocally connected, show the same topographic organization in "eyeless" animals as in control chickens raised under the same conditions. This clearly indicates that the topographic organization of the chicken optic tectum is independently specified and is not contingent upon the input that it receives from the retina.

Afferent Pathways↗