Neurochemical characterization of specific cell populations in the macaque monkey hippocampus.
Item
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Title
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Neurochemical characterization of specific cell populations in the macaque monkey hippocampus.
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Identifier
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AAI9417508
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identifier
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9417508
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Creator
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Siegel, Steven J.
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Contributor
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Adviser: John H. Morrison
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Date
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1994
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Language
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English
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Publisher
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City University of New York.
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Subject
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Biology, Neuroscience
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Abstract
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The current study investigates various neurochemical characteristics of identified neuronal populations in the monkey hippocampus with respect to normal distribution patterns, developmental regulation and the effects of environmental perturbations. The hippocampal formation was selected for investigation following initial efforts to identify neuroanatomic correlates of behavioral abnormalities as a result of social deprivation. To this end, chapter 3 describes an increase in the level of immunoreactivity for a nonphosphorylated epitope of neurofilament proteins in the granule cell layer of the dentate gyrus in juvenile monkeys which experienced social deprivation as compared with age matched socially reared animals. Following this observation, studies were designed to determine whether such a pattern represented a delayed developmental progression or the induction of a neuropathologic process. Observations in 15 monkeys ranging from 9 days of age to 9 months of age indicate that the pattern of neurofilament immunoreactivity seen in socially deprived animals does not exist normally in juvenile animals suggesting that such a pattern may represent a neuropathologic alteration reminiscent of the type of cytoskeletal alterations seen following a variety of insults to the nervous system. It has been previously hypothesized that such cytoskeletal changes in discrete neuronal populations may be mediated by excitotoxic mechanisms. Therefore, in order to further understand the factors which contribute to cell-type specific alterations following particular insults to the nervous system, investigations were initiated to examine the regional, cellular and ultrastructural distribution patterns of several excitatory amino acid receptor subunits. These studies indicate that immunoreactivity for the excitatory amino acid receptor subunits GluR2, GluR5-7 and NMDAR1 are ubiquitously distributed throughout all portions of the hippocampus and furthermore that virtually every neuronal profile in the hippocampus which is immunoreactive for one of these sets of subunits also contains the others. However, ultrastructural data from work described in this thesis as well as in related studies indicate that certain excitatory circuits within the hippocampus are mediated preferentially if not exclusively by a subset of ionotropic excitatory amino acid receptor subtypes. Specifically, synapses between mossy fiber axons of dentate gyrus granule cells and thorny excrescences on dendrites of CA3 pyramidal cells appear to be immunoreactive for GluR2 and GluR5-7 (Good et al., 1993), but lack immunoreactivity for NMDAR1. This pattern was markedly different than the pattern characterizing synapses on more distally located dendritic specializations of CA3 pyramidal cells, which receive associational/commissural excitatory inputs, where all three receptor subtypes were located. Such circuit specific distributions for the various receptor subtypes may contribute to differential vulnerability seen in response to a variety of insults to the nervous system including social deprivation.
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Type
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dissertation
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Source
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PQT Legacy CUNY.xlsx
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degree
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Ph.D.
