TY - JOUR T1 - Corticotropin releasing factor receptor-1 neurons in the lateral amygdala display selective sensitivity to acute and chronic ethanol exposure JF - eneuro JO - eNeuro DO - 10.1523/ENEURO.0420-19.2020 SP - ENEURO.0420-19.2020 AU - AE Agoglia AU - M Zhu AU - R Ying AU - H Sidhu AU - LA Natividad AU - SA Wolfe AU - MW Buczynski AU - C Contet AU - LH Parsons AU - M Roberto AU - MA Herman Y1 - 2020/02/06 UR - http://www.eneuro.org/content/early/2020/02/06/ENEURO.0420-19.2020.abstract N2 - 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 (CRF1+) and non-expressing (CRF1-) LA neurons and investigate the effects of acute and chronic ethanol exposure on these populations. The CRF1+ population was found to be comprised predominantly of glutamatergic projection neurons with a minority subpopulation of interneurons. CRF1+ neurons exhibited a tonic conductance that was insensitive to acute ethanol. CRF1- neurons did not display a basal tonic conductance, but application of acute ethanol induced a δ GABAA receptor subunit-dependent tonic conductance and enhanced phasic GABA release onto these cells. Chronic ethanol increased CRF1+ neuronal excitability but did not significantly alter phasic or tonic GABA signaling in either CRF1+ 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 sensitivity of GABA or glutamate to acute ethanol-induced increases in transmitter release. Together, these results provide the first characterization of the CRF1+ population of LA neurons and suggest mechanisms for differential acute ethanol sensitivity within this region.SIGNIFICANCE STATEMENT The corticotropin releasing factor (CRF) system is a critical component of the stress network and has been implicated in psychiatric disorders including addiction, anxiety, and depression. The present study examines CRF receptor-1 (CRF1) lateral amygdala (LA) neurons and reports differential inhibitory control and acute ethanol effects of CRF1 LA neurons as compared to the unlabeled (CRF1-) population. An improved understanding of CRF1 amygdala circuitry and the selective sensitivity of that circuitry to ethanol represents an important step in identifying brain region-specific neuroadaptations that occur with ethanol exposure. The present findings also have broad implications, including potential relevance to the role of CRF1 circuitry in other contexts that may provide insight into other disorders involving amygdala dysfunction, including anxiety and depression. ER -