Corticotropin-releasing factor receptor-1 neurons in the lateral amygdala display selective sensitivity to acute and chronic ethanol exposure

Abstract

The lateral amygdala (LA) serves as the point of entry for sensory information within the amygdala complex, a structure that plays a critical role in emotional processes and has been implicated in alcohol use disorders. Within the amygdala, the corticotropin-releasing factor (CRF) system has been shown to mediate some of the effects of both stress and ethanol, but the effects of ethanol on specific CRF1 receptor circuits in the amygdala have not been fully established. We used male CRF1:GFP reporter mice to characterize CRF1-expressing (CRF11) and nonex-pressing (CRF1) LA neurons and investigate the effects of acute and chronic ethanol exposure on these popula-tions. The CRF11 population was found to be composed predominantly of glutamatergic projection neurons with a minority subpopulation of interneurons. CRF11 neurons exhibited a tonic conductance that was insensitive to acute ethanol. CRF1 neurons did not display a basal tonic conductance, but the application of acute ethanol induced a d GABAA receptor subunit-dependent tonic conductance and enhanced phasic GABA release onto these cells. Chronic ethanol increased CRF11 neuronal excitability but did not significantly alter phasic or tonic GABA signaling in either CRF11 or CRF1 cells. Chronic ethanol and withdrawal also did not alter basal extracellular GABA or glutamate transmitter levels in the LA/BLA and did not alter the sensitivity of GABA or glutamate to acute ethanol-in-duced increases in transmitter release. Together, these results provide the first characterization of the CRF11 population of LA neurons and suggest mechanisms for differential acute ethanol sensitivity within this region.