Optogenetic inhibition of light‐captured alcohol‐taking striatal engrams facilitates extinction and suppresses reinstatement

Abstract

AbstractBackgroundAlcohol use disorder (AUD) is a complex condition, and it remains unclear which specific neuronal substrates mediate alcohol‐seeking and ‐taking behaviors. Engram cells and their related ensembles, which encode learning and memory, may play a role in this process. We aimed to assess the precise neural substrates underlying alcohol‐seeking and ‐taking behaviors and determine how they may affect one another.MethodsUsing FLiCRE (Fast Light and Calcium‐Regulated Expression; a newly developed technique which permits the trapping of acutely activated neuronal ensembles) and operant self‐administration (OSA), we tagged striatal neurons activated during alcohol‐taking behaviors. We used FLiCRE to express an inhibitory halorhodopsin in alcohol‐taking neurons, permitting loss‐of‐function manipulations.ResultsWe found that the inhibition of OSA‐tagged alcohol‐taking neurons decreased both alcohol‐seeking and ‐taking behaviors in future OSA trials. In addition, optogenetic inhibition of these OSA‐tagged alcohol‐taking neurons during extinction training facilitated the extinction of alcohol‐seeking behaviors. Furthermore, inhibition of these OSA‐tagged alcohol‐taking neurons suppressed the reinstatement of alcohol‐seeking behaviors, but, interestingly, it did not significantly suppress alcohol‐taking behaviors during reinstatement.ConclusionsOur findings suggest that alcohol‐taking neurons are crucial for future alcohol‐seeking behaviors during extinction and reinstatement. These results may help in the development of new therapeutic approaches to enhance extinction and suppress relapse in individuals with AUD.