Author:
Dao Nigel C.,Brockway Dakota F.,Suresh Nair Malini,Sicher Avery R.,Crowley Nicole A.
Abstract
AbstractSomatostatin (SST) neurons have been implicated in a variety of neuropsychiatric disorders such as depression and anxiety, but their role in substance use disorders, including alcohol use disorder (AUD), is not fully characterized. Here, we found that repeated cycles of alcohol binge drinking via the Drinking-in-the-Dark (DID) model led to hypoactivity of SST neurons in the prelimbic (PL) cortex by diminishing their action potential firing capacity and excitatory/inhibitory transmission dynamic. We examined their role in regulating alcohol consumption via bidirectional chemogenetic manipulation. Both hM3Dq-induced excitation and KORD-induced silencing of PL SST neurons reduced alcohol binge drinking in males and females, with no effect on sucrose consumption. Alcohol binge drinking disinhibited pyramidal neurons by augmenting SST neurons-mediated GABA release and synaptic strength onto other GABAergic populations and reducing spontaneous inhibitory transmission onto pyramidal neurons. Pyramidal neurons additionally displayed increased intrinsic excitability. Direct inhibition of PL pyramidal neurons via hM4Di was sufficient to reduce alcohol binge drinking. Together these data revealed an SST-mediated microcircuit in the PL that modulates the inhibitory dynamics of pyramidal neurons, a major source of output to subcortical targets to drive reward-seeking behaviors and emotional response.
Funder
U.S. Department of Health & Human Services | NIH | National Institute on Alcohol Abuse and Alcoholism
Brain and Behavior Research Foundation
Penn State | Social Science Research Institute, Pennsylvania State University
Publisher
Springer Science and Business Media LLC
Subject
Psychiatry and Mental health,Pharmacology
Reference59 articles.
1. National Institute of Alcohol Abuse and Alcoholism. Drinking Levels Defined. National Institute of Alcohol Abuse and Alcoholism. https://www.niaaa.nih.gov/alcohol-health/overview-alcohol-consumption/moderate-binge-drinking (2020).
2. American Psychiatric Association. Diagnostic and Statistical Manual of Mental Disorders, 5th. Ed. American Psychiatric Publishing (2013).
3. National Institute of Alcohol Abuse and Alcoholism. Alcohol Facts and Statistics. NIAAA [WWW Document]. https://www.niaaa.nih.gov/publications/brochures-and-fact-sheets/alcohol-facts-and-statistics (2020).
4. Wilsnack RW, Wilsnack SC, Gmel G, Kantor LW. Gender differences in binge drinking prevalence, predictors, and consequences. Alcohol Res Curr Rev. 2017;39:57–76.
5. Abrahao KP, Salinas AG, Lovinger DM. Alcohol and the brain: neuronal molecular targets, synapses, and circuits. Neuron. 2017;96:1223–38.
Cited by
26 articles.
订阅此论文施引文献
订阅此论文施引文献,注册后可以免费订阅5篇论文的施引文献,订阅后可以查看论文全部施引文献