A cortical-brainstem circuit predicts and governs compulsive alcohol drinking

By Cody A. Siciliano, Habiba Noamany, Chia-Jung Chang, Alex R Brown, Xinhong Chen, Daniel Leible, Jennifer J Lee, Joyce Wang, Amanda N Vernon, Caitlin M. Vander Weele and 3 more. 2019

168 citations recorded by the source corpus.

A brain circuit to control alcohol intake Most people are exposed to alcohol at some point in their lives, but only a small fraction will develop a compulsive drinking disorder. Siciliano et al. first established a behavioral measure to assess how predisposition interacts with experience to produce compulsive drinking in a subset of mice (see the Perspective by Nixon and Mangieri). In search of the underlying neurobiological mechanism, they discovered that a discrete circuit between the medial prefrontal cortex and brainstem is central for the development of compulsive drinking. This circuit serves as both a biomarker for the development of compulsive drinking and a driver of its expression. It can bidirectionally control compulsive behavior by mitigating or mimicking punishment signals. Science, this issue p. 1008; see also p. 947 Cortical representation of initial alcohol exposure is a biomarker for future development of compulsive drinking. What individual differences in neural activity predict the future escalation of alcohol drinking from casual to compulsive? The neurobiological mechanisms that gate the transition from moderate to compulsive drinking remain poorly understood. We longitudinally tracked the development of compulsive drinking across a binge-drinking experience in male mice. Binge drinking unmasked individual differences, revealing latent traits in alcohol consumption and compulsive drinking despite equal prior exposure to alcohol. Distinct neural activity signatures of cortical neurons projecting to the brainstem before binge drinking predicted the ultimate emergence of compulsivity. Mimicry of activity patterns that predicted drinking phenotypes was sufficient to bidirectionally modulate drinking. Our results provide a mechanistic explanation for individual variance in vulnerability to compulsive alcohol drinking.

Subfields: Cellular and Molecular Neuroscience, Cognitive Neuroscience, Pharmacology

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Citations in the corpus

A modeling framework for adaptive lifelong learning with transfer and savings through gating in the prefrontal cortex (2020, background): “Although studies have most clearly linked perseverative abnormalities to dlPFC, similar abnormalities can be observed in compulsive behaviors like alcohol consumption, which depend on strategies generated by the mPFC that predict individual behavioral patterns (72).”