Corticotropin-releasing factor (CRF) is the major mediator of stress responses in the brain and has been implicated in both normal fear and pathological anxiety. The extended amygdala, a functional-anatomical continuum in the basal forebrain, contains the CRF systems considered most responsible for mediating the behavioral aspects of fear and anxiety produced by stressful situations. Recent progress in the characterization of CRF mechanisms across the brain suggests that two dichotomous anatomical CRF systems, mediated by specific CRF1 versus CRF2a receptor subtypes, modulate unique facets of the stress response. The extended amygdala represents one of few brain regions in which both hypothesized CRF receptor systems are present to a significant degree; yet little detailed knowledge exists regarding CRF receptor systems in this region. The experiments in this proposal are intended to provide basic knowledge both about CRF receptor systems that contribute to fear and anxiety as well as about the organization of the extended amygdala and neighboring caudal accumbens shell. Our combined anatomical and behavioral approach reflects our appreciation of the inter-dependency of form and function, and that a thorough understanding of any neural system requires examination of both.
Our specific aims are: 1) To describe the anatomical organization of CRF receptor systems in extended amygdala and caudal accumbens shell. The proposed experiments will describe: a) the distribution and co-localization of CRF receptor subtypes (CRF1 and CRF2a receptors) within extended amygdala and caudal accumbens shell regions (immunohistochemistry combined with in situ hybridization), b) the afferent pathways delivering CRF peptide to extended amygdala and caudal shell (retrograde tracer combined with in situ hybridization), and c) the efferent pathways of extended amygdala and caudal shell cells containing CRF1 versus CRF2a receptors (retrograde tracer combined with in situ hybridization). 2) To determine the roles of CRF receptors in the extended amygdala and caudal accumbens shell in the behavioral expression of fear and anxiety. Proposed experiments will examine how fear and anxiety behavior are modulated within specific regions of extended amygdala and caudal accumbens shell by: a) non-specific CRF ligands, and b) subtype-specific ligands for CRF1 versus CRF2a receptors.
| Zahm, Daniel S; Trimble, Michael (2008) The dopaminergic projection system, basal forebrain macrosystems, and conditioned stimuli. CNS Spectr 13:32-40 |
