The goal of this project is two-fold: 1) to increase our understanding of the neuronal circuitry critical to stress activation, stress termination, and the differential stress responsiveness across the circadian rhythm of the rat; and 2) to understand how this circuitry may be differentially activated as a function of the nature of the stressor (i.e., the ability of the animal to cope with it) and as a function of individual differences. Thus, we plan to examine, as a prototypical activational pathway, the catecholaminergic inputs which impinge upon the final common path of stress integration in the brain--the hypothalamic neurons which express corticotropin releasing hormone (CRH). We plan to ask whether the CRH neurons have compartments which can be distinguished based on gene expression, and whether these compartments are differentially responsive to differentially responsive to different stressors. In terms of stress inhibition, we shall focus on the role of the inhibitory neurotransmitter, gamma-amino-butyric acid (GABA) as a mediator of both glucocorticoid-dependent and independent negative feedback. Finally, in the anatomical studies, we shall study the role of the suprachiasmatic nucleus (SCN) as a structure which may adjust the """"""""gain"""""""" on the stress response as a function of the circadian rhythm, regulating not only the basal tone, but also stress responsiveness and stress termination. At the more behavioral level, we shall use a number of well-established models to look at how brain circuits, or specific modules within them, may become differentially activated as a function of the degree of control that the animal has over the stressor (executive vs. yoked model), or the outcome of a social stress (victory vs. defeat following an agonistic encounter). Finally, we shall ask whether animals which exhibit individual differences in stress responsiveness either at the endocrine level (Fisher vs. Lewis rats) or at the behavioral level (High responders vs. Low responders) do so because they are activating different modules of these stress-responsive neuronal circuits. Together, this set of studies should increase our understanding of the neuronal underpinning of stress responsiveness and coping with stress.
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