Organization /Function of Extended Amygdala CRF Systems

Saint Louis University, Saint Louis MO

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Abstract

DESCRIPTION (provided by applicant): Corticotropin-releasing factor (CRF) is currently considered to play a major role in the mediation of stress responses, and thus is implicated in fear, anxiety, and drug addiction. Two regions of intense CRF activity include the extended amygdala and nucleus accumbens shell, which in addition to their acknowledged roles in drug addiction are also important in mediating states of fear and anxiety. Although actions of CRF are thought to be mediated by at least two systems (through CRF1 versus CRF2 receptor subtypes) with distinct distribution patterns throughout the brain, the extended amygdala/caudal accumbens shell represent one of the few regions of high CRF receptor subtype overlap. The goal of Aim 1 is to reveal the organization of CRF systems within the extended amygdala and caudal accumbens shell. First the co-localization of CRF 1 and CRF2 receptor subtypes on neurons within the extended amygdala and caudal accumbens shell will be examined using combined in situ hybridization and immunohistochemistry. Second, the efferent projections of CRF receptor expressing cells to output structures, as well as intrinsic structures, of the extended amygdala and caudal shell will be compared with combined retrograde tracing and immunohistochemistry or in situ hybridization. The goal of Aim 2 is to determine the function of CRF receptors in the extended amygdala and caudal shell in mediating states of fear and anxiety. The behavioral consequences of activation or blockade of general as well as specific (CRF1 versus CRF2) CRF receptor agonist and antagonist microinjections into specific regions of the extended amygdala and caudal accumbens shell will be determined in the elevated plus-maze and defensive burying paradigms.