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R S Nowakowski

Publications and source records attributed to R S Nowakowski.

60 records · Page 4Linked to original sources

The time of origin of neurons in the hippocampal region of the rhesus monkey.

The time of origin of neurons in the hippocampal region was determined in a series of rhesus monkeys, each of which had been exposed to a pulse of tritiated thymidine (3H-TdR) at a different time during ontogeny and sacrificed between the second and fifth month after birth. No heavily labeled cells were found in the hippocampal region of animals exposed to 3H-TdR before embryonic day 33 (E33). Exposure to 3H-TdR given at E36 labels a few neurons in the deepest layers of the entorhinal area, and 3H-TdR given at E38 labels a small number of neurons in all hippocampal subdivisions. Although the first neurons are generated almost simultaneously throughout the hippocampal region, the proliferation ceases at a different time in each subdivision. The last neurons destined for the entorhinal area and presubiculum are generated between E70 and E75, whereas the last parasubicular neurons are generated between E75 and E80. The production of neurons that form the subiculum ends about two weeks earlier, between E56 and E65. Within the hippocampus, genesis of pyramidal cells ends between E70 and E80 in area CA1, between E56 and E65 in area CA2, between E65 and E80 in area CA1, between E56 and E65 in area CA2, between E65 and E70 in area CA3, and between E75 and E80 in area CA4. In contrast, the genesis of granule cells of the fascia dentata is considerably prolonged. It continues throughout the second half of gestation, declines steadily in the course of the first postnatal month, and tapers off during the next 2 months. There is a distinct inside-to-outside spatiotemporal gradient in the parahippocampal formation and in the stratum pyramidale of both the subiculum and hippocampus. In contrast, the spatiotemporal pattern of granule cell origin in the dentate gyrus is outside-to-inside. Furthermore, granule cells generated between E36 and E80 are distributed in a distinct suprapyramidal-to-infrapyramidal gradient, whereas those generated at later ages are distributed evenly throughout the fascia dentata. Correlation of the present findings with histological data on hippocampal neurogenesis in the human brain demonstrates that the timing and sequence of developmental events as well as spatiotemporal gradients are similar in both primate species.

Aging↗

The site of origin and route and rate of migration of neurons to the hippocampal region of the rhesus monkey.

The site of origin and route and rate of migration of neurons in the developing hippocampal region of the rhesus monkey were studied with tritiated thymidine (3H-TdR) autoradiography. Analysis of specimens sacrificed approximately 1 hour after exposure to 3H-TdR shows that the neurons destined for the hippocampus and subiculum are generated exclusively in the ventricular zone lining the medial wall of the lateral cerebral ventricle. In contrast, neurons of the parahippocampal formation are generated in two proliferative zones: The majority of neurons destined for the lamina principalis interna arise from the ventricular zone, whereas most of those destined for the lamina principalis externa originate from the subventricular zone. The neurons of the dentate gyrus are also generated in two locations: in the ventricular zone (between E38 and E85) and within the prospective hilus of the dentate gyrus (from E58 up to approximately 3 months after birth). Analysis of specimens sacrificed at progressively longer intervals after exposure to 3H-TdR indicates that neurons destined for all of the subdivisions of the hippocampal region (except those cells generated in the hilus of the dentate gyrus) migrate through the intermediate zone, bypassing previously generated neurons on their way to the superficial limits of the developing cortical plate. Estimated migration rates are approximately 15 micrometer/day in the sector of the hippocampal formation, about 100 micrometer/day in the parahippocampal formation, and about 15 micrometer/day in the region of adjacent neocortex. Thus simultaneously generated neurons destined for three distinct cytoarchitectonic areas have significantly different rates of cell migration. These differences are unrelated to the length of cell trajectories and may depend on the mechanism of cell translocation and/or the timing of signals that initiate cell movement. The differential rate of migration indicates that the fate of postmitotic cells may be determined before they have reached their final destination.

Aging↗

The mode of migration of neurons to the hippocampus: a Golgi and electron microscopic analysis in foetal rhesus monkey.

The mode of neuron migration from the site of their origin in the ventricular zone to area CA1 of the hippocampus was analysed with Golgi and electron microscopic methods during the first half of gestation in the foetal rhesus monkey. In the inner portion of the intermediate zone, the migrating cells have a bipolar form with one, or oaccasionally two, leading processes which do not reach the ammonic plate and with a single trailing process which usually ends within the intermediate zone. Both the nucleus and the cytoplasm of the migrating cells are relatively electron-dense and the latter contains organelles typical of young neurons as described in other brain regions. Analysis of electron micrographs from serial sections reveals that the length of the somata and of the leading and trailing processes of the migrating neurons is apposed to fascicles of radially oriented, electron-lucent, microtubule-filled fibres which are ultrastructurally similar to the radial glial fibres of the neocortex and to the Bergmann glial fibres of the cerebellum. The close (20 nm) apposition between the membranes of the migrating cell and the radial fibre is maintained even in areas where the fibres bend or curve tortuously. Migrating neurons situated at progressively more superficial levels of the intermediate zone become progressively more differentiated and complex. Thus, in the outer portion of the intermediate zone, the migrating cells acquire several additional cytoplasmic processes and occasionally a long thin axon-like process which courses into the incipient alveus. These cells have somewhat larger somata and less electron-dense nuclei and cytoplasm than the migrating neurons still situated in the inner part of the intermediate zone. Cells close to the ammonic plate usually have one to three cytoplasmic processes that enter the ammonic plate and terminate near their presumed final position. Migrating neurons situated at the lower border of the ammonic plate have a single large apical process which intermingles with neurons already in their final position and which sometimes traverses the ammonic plate. The apposition of the migrating neurons to the radial glial processes becomes less explicit as the cell soma enters the ammonic plate, reflecting the more complex three-dimensional intercellular relationships. However, the present analysis indicates that during the middle and late stages of neuronal migration to the hippocampus radial glial fibres may guide postmitotic young neurons across the intermediate zone to the ammonic plate in the same way that they guide neurons migrating to the superficial and middle layers of the neocortical plate.

Animals↗

A gradient in the duration of the G1 phase in the murine neocortical proliferative epithelium.

Neuronogenesis in the neocortical pseudostratified ventricular epithelium (PVE) is initiated rostrolaterally and progresses caudo-medially as development progresses. Here we have measured the cytokinetic parameters and the fractional neuronal output parameter, Q, of laterally located early-maturing regions over the principal embryonic days (E12-E15) of neocortical neuronogenesis in the mouse. These measures are compared with ones previously made of a medial, late-maturing portion of the PVE. Laterally, as medially, the duration of the neuronogenetic interval is 6 days and comprises 11 integer cell cycles. Also, in both lateral and medial areas the length of G1 phase (TG1) increases nearly 4-fold and is the only cell cycle parameter to change. Q progresses essentially identically laterally and medially with respect to the succession of integer cell cycles. Most importantly, from E12 to E13 there is a steeply declining lateral to medial gradient in TG1. The gradient is due both to the lateral to medial graded stage of neuronogenesis and to the stepwise increase in TG1 with each integer cycle during the neuronogenetic interval. To our knowledge this gradient in TG1 of the cerebral PVE is the first cell biological gradient to be demonstrated experimentally in such an extensive proliferative epithelial sheet. We suggest that this gradient in TG1 is the cellular mechanism for positionally encoding a protomap of the neocortex within the PVE.

Animals↗