The center of the emotional universe: Alcohol, stress, and CRF1 amygdala circuitry

Abstract

The commonalities between different phases of stress and alcohol use as well as the high comorbidity between alcohol use disorders (AUDs) and anxiety disorders suggest common underlying cellular mechanisms governing the rewarding and aversive aspects of these related conditions. As an integrative center that assigns emotional salience to a wide variety of internal and external stimuli, the amygdala complex plays a major role in how alcohol and stress influence cellular physiology to produce disordered behavior. Previous work has illustrated the broad role of the amygdala in alcohol, stress, and anxiety. However, the challenge of current and future studies is to identify the specific dysregulations that occur within distinct amygdala circuits and subpopulations and the commonalities between these alterations in each disorder, with the long-term goal of identifying potential targets for therapeutic intervention. Specific intra-amygdala circuits and cell type-specific subpopulations are emerging as critical targets for stress- and alcohol-induced plasticity, chief among them the corticotropin releasing factor (CRF) and CRF receptor 1 (CRF1) system. CRF and CRF1 have been implicated in the effects of alcohol in several amygdala nuclei, including the basolateral (BLA) and central amygdala (CeA); however, the precise circuitry involved in these effects and the role of these circuits in stress and anxiety are only beginning to be understood.

Keywords: Alcohol; Amygdala; Anxiety; Fear; Stress.

Figure 1

CRF1 subpopulations in the amygdala complex. A. GFP expression in CRF1-containing neurons in the amygdala, including discrete populations in the LA. BM, Imp, IN, and CeA_M. Scale bar = 400 μm. B. Schematic diagram of proposed CRF1 circuitry showing inter- and intranuclear connections. BL: basolateral; BM: basomedial; CeA_L: lateral central amygdala; CeA_M: medial central amygdala; Imp: medial paracapsular intercalated; IN main intercalated; LA lateral amygdala.