Student Theses and Dissertations


Kara Pham

Date of Award


Document Type


Degree Name

Doctor of Philosophy (PhD)

RU Laboratory

McEwen Laboratory


The addition of new neurons continues in the dentate gyrus of the adult rat, and this process has been previously shown to be regulated by adrenal steroid hormones, Nmethyl- D-aspartate (NMDA) receptor activity, psychosocial stress and learning and memory. Repeated restraint stress is known to induce neuroanatomical changes in the hippocampus, such as dendritic remodeling in CA3 neurons and mossy fiber terminal rearrangement, and these alterations are reversible, suggesting that the hippocampal system experiences a certain degree of plasticity in response to stress. This dissertation examines the effects of chronic restraint stress on several parameters of hippocampal plasticity, including dentate gyrus neurogenesis, polysialic acid neural cell adhesion molecule (PSA-NCAM) expression and neuronal excitability. In addition, the learning and memory process is dissected using a contextual fear conditioning paradigm in order to identify the component that can affect hippocampal cell proliferation. The results presented demonstrate that repeated stress, which activates the hypothalamic-pituitary-adrenal (HPA) axis and leads to increased glucocorticoid and glutamate release, can inhibit hippocampal neurogenesis, reduce dentate gyrus cell numbers and volume, enhance the expression of PSA-NCAM and transiently increase the synaptic response in the dentate gyrus after perforant path stimulation. Contextual fear conditioning was also shown to temporarily decrease cell proliferation in the dentate gyrus. Taken together, the results suggest that the hippocampus is capable of responding to an animal's experiences with stress and learning tasks by inducing plasticity events that can revert to baseline, such as synaptic enhancement, dendritic remodeling, and PSA-NCAM elevation. However, when the stress was endured for extended periods, the morphological response became more extreme, exhibiting reductions in neurogenesis, total granule neuron numbers and granule cell layer volume. At this level of stress, PSANCAM expression was no longer enhanced, implying that the dentate gyrus had acquired a more stable condition and one that is perhaps more vulnerable to permanent changes.


A thesis presented to the faculty of The Rockefeller University in partial fulfillment of the requirements for the degree of Doctor of Philosophy

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