RT Journal Article SR Electronic T1 Chronic Intermittent Ethanol Exposure Dysregulates Nucleus Basalis Magnocellularis Afferents in the Basolateral Amygdala JF eneuro JO eNeuro FD Society for Neuroscience SP ENEURO.0164-22.2022 DO 10.1523/ENEURO.0164-22.2022 VO 9 IS 6 A1 Sarah E. Sizer A1 Michaela E. Price A1 Brian C. Parrish A1 Samuel H. Barth A1 Chelcie F. Heaney A1 Kimberly F. Raab-Graham A1 Brian A. McCool YR 2022 UL http://www.eneuro.org/content/9/6/ENEURO.0164-22.2022.abstract AB Nucleus basalis magnocellularis (NBM) cholinergic projections to the basolateral amygdala (BLA) regulate the acquisition and consolidation of fear-like and anxiety-like behaviors. However, it is unclear whether the alterations in the NBM-BLA circuit promote negative affect during ethanol withdrawal (WD). Therefore, we performed ex vivo whole-cell patch-clamp electrophysiology in both the NBM and the BLA of male Sprague Dawley rats following 10 d of chronic intermittent ethanol (CIE) exposure and 24 h of WD. We found that CIE exposure and withdrawal enhanced the neuronal excitability of NBM putative “cholinergic” neurons. We subsequently used optogenetics to directly manipulate NBM terminal activity within the BLA and measure cholinergic modulation of glutamatergic afferents and BLA pyramidal neurons. Our findings indicate that CIE and withdrawal upregulate NBM cholinergic facilitation of glutamate release via activation of presynaptic nicotinic acetylcholine receptors (AChRs). Ethanol withdrawal-induced increases in NBM terminal activity also enhance BLA pyramidal neuron firing. Collectively, our results provide a novel characterization of the NBM-BLA circuit and suggest that CIE-dependent modifications to NBM afferents enhance BLA pyramidal neuron activity during ethanol withdrawal.