Alcohol drinking is associated with greater calcium activity in mouse central amygdala dynorphin-expressing neurons

Abstract

Alcohol use disorder (AUD) is a chronic disease that poses significant economic burden and health risks. It is pivotal to better understand brain mechanisms engaged by alcohol that promote misuse. The central amygdala (CeA) has emerged as a key mediator of excessive preclinical alcohol consumption. A dynorphin-expressing subpopulation within the CeA (CeADyn) has been implicated in excessive alcohol drinking, yet how cellular activity of CeADyn neurons relates to ongoing alcohol drinking is not well-understood. The current study interrogated the engagement of CeADyn neurons in male and female mice during voluntary alcohol consumption using fiber photometry and compared this cellular response with that of other solutions having similar motivational and/or taste characteristics. Activity of a calcium sensor, GCaMP7f, expressed in mouse CeADyn neurons was recorded and time-locked to bouts of drinking. Multilevel linear mixed modeling was applied to better resolve focal effects from complex data. These analyses revealed a relatively large increase in CeADyn neuron calcium transients after bouts of alcohol drinking compared to water or sucrose drinking, indicating these neurons are uniquely engaged during alcohol consumption. Drinking behavior unique to alcohol (i.e., longer bout durations) did not fully explain signal differences between alcohol and other solutions nor did the relatively increased alcohol response diminish over time. No other conditions or solutions tested reproduced the pronounced change in CeADyn activity associated with alcohol drinking. These findings, collectively, support the presence of a unique functional signature for alcohol in a cell population known to control excessive alcohol drinking. HighlightsO_LICentral amygdala dynorphin cells (CeADyn) are firmly implicated in alcohol misuse. C_LIO_LICeADyn neuron activity was higher when mice drank alcohol versus other solutions. C_LIO_LINeither how mice drank alcohol nor motivational states could explain this activity. C_LIO_LICeADyn neurons having uniquely high alcohol responses may underlie AUD development. C_LI