Chronic Glucocorticoid Effects in Prefrontal Cortex

点击翻译按钮获取中文摘要

DESCRIPTION (provided by applicant): Chronic stress produces deficits in cognition accompanied by alterations in neural chemistry and morphology. For example, both stress and chronic administration of corticosterone produce dendritic atrophy in hippocampal neurons. Prefrontal cortex is also a target for glucocorticoids involved in the stress response shows neurochemical changes in response to stress and plays a role in many of the cognitive processes that undergo stress-induced alterations. Thus, changes in prefrontal cortex may mediate some stress- and glucocorticoid-induced cognitive deficits. To determine if glucocorticoid-induced morphological changes also occur in medial prefrontal cortex, I assessed the effects of chronic corticosterone administration on dendritic morphology in this corticolimbic structure. Previously, I demonstrated that chronic corticosterone administration resulted in a significant redistribution of apical dendrites of lamina II-III pyramidal neurons in medial prefrontal cortex of rats: amount of dendritic material proximal to the soma was increased, while distal dendritic material was decreased relative to controls. The experiments proposed here will lay the groundwork necessary to begin to assess the functional significance and mechanisms of this dendritic reorganization. To determine the minimum duration of chronic mild stress necessary to alter the structure of pyramidal neurons in medial prefrontal cortex, I will assess the effects of varying durations of chronic restraint stress on dendritic arborization of layer II-III pyramidal neurons in medial prefrontal cortex. To determine whether stress-induced changes in prefrontal cortex are mediated by corticosterone, I will assess whether administration of a corticosterone blocker prevents stress-induced changes in dendritic morphology of layer II-III pyramidal neurons in medial prefrontal cortex. Finally, to determine whether stress alters a prefrontally mediated behavior, I will assess the effect of chronic restraint stress on extinction of fear conditioning