RT Journal Article SR Electronic T1 Molecular, morphological, and functional characterization of corticotropin-releasing factor receptor 1-expressing neurons in the central nucleus of the amygdala JF eneuro JO eNeuro FD Society for Neuroscience SP ENEURO.0087-19.2019 DO 10.1523/ENEURO.0087-19.2019 A1 S. A. Wolfe A1 H. Sidhu A1 R. R. Patel A1 M. Kreifeldt A1 S. R. D’Ambrosio A1 C. Contet A1 M. Roberto YR 2019 UL http://www.eneuro.org/content/early/2019/06/05/ENEURO.0087-19.2019.abstract AB The central nucleus of the amygdala (CeA) is a brain region implicated in anxiety, stress-related disorders and the reinforcing effects of drugs of abuse. Corticotropin-releasing factor (CRF, Crh) acting at cognate type 1 receptors (CRF1, Crhr1) modulates inhibitory and excitatory synaptic transmission in the CeA. Here, we used CRF1:GFP reporter mice to characterize the morphological, neurochemical and electrophysiological properties of CRF1 expressing (CRF1+) and CRF1 non-expressing (CRF1-) neurons in the CeA. We assessed these two neuronal populations for distinctions in the expression of GABAergic subpopulation markers and neuropeptides, dendritic spine density and morphology, and excitatory transmission. We observed that CeA CRF1+ neurons are GABAergic but do not segregate with calbindin, calretinin, parvalbumin, or PKCδ. Among the neuropeptides analyzed, Penk and Sst had the highest percentage of co-expression with Crhr1 in both the medial and lateral CeA subdivisions. Additionally, CeA CRF1+ neurons had a lower density of dendritic spines, which was offset by a higher proportion of mature spines compared to neighboring CRF1- neurons. Accordingly, there was no difference in basal spontaneous glutamatergic transmission between the two populations. Application of CRF increased overall vescicular glutamate release onto both CRF1+ and CRF1- neurons, and does not effect amplitude or kinetics of excitatory post-synaptic currents in either population. These novel data highlight important differences in the neurochemical make-up and morphology of CRF1+ compared to CRF1- neurons, which may have important implications for the transduction of CRF signaling in the CeA.SIGNIFICANCE Corticotropin-releasing factor (CRF) is involved in emotional regulation via hypothalamic and amygdalar circuits, and is implicated in several psychiatric disorders including anxiety, depression, addiction, posttraumatic stress disorder, and eating disorders. Our novel identification of unique molecular, morphological and functional properties to distinguishing CRF1+ neurons in the central amygdala represents a critical step in understanding the cellular role and dysregulation of the CRF system in pathological conditions.