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bioRxiv · 10.1101/2024.06.02.597021

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

Vierkant, V.·Xie, X.·Huang, Z.·He, L.·Bancroft, E.·Wang, X.·Srinivasan, R.·Zhou, Y.·Wang, J.
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Abstract

BackgroundAlcohol 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.

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Vierkant, V., Xie, X., Huang, Z., He, L., Bancroft, E., Wang, X., Srinivasan, R., Zhou, Y., Wang, J.. 2024-06-02. Optogenetic inhibition of light-captured alcohol-taking striatal engrams facilitates extinction and suppresses reinstatement. https://doi.org/10.1101/2024.06.02.597021

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