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An orbitocortical-thalamic circuit suppresses binge alcohol-drinking
P Gimenez-Gomez1,2, T Le1,2, M Zinter1
1Brudnick Neuropsychiatric Research Institute, Department of Neurobiology, University of Massachusetts Chan Medical School, Worcester, MA 01605, USA.
Biorxiv : the Preprint Server for Biology
|July 15, 2024
Summary
Scientists discovered a specific brain circuit in the medial orbitofrontal cortex that naturally limits alcohol consumption. This neural ensemble suppresses binge drinking, offering new targets for alcohol abuse interventions.
Area of Science:
- Neuroscience
- Addiction Research
- Behavioral Science
Background:
- Alcohol consumption is a major global health issue with significant mortality.
- The prefrontal cortex, crucial for inhibitory control, shows dysregulation in alcohol abuse.
- The existence of endogenous mechanisms within the prefrontal cortex to limit alcohol intake was previously unknown.
Purpose of the Study:
- To identify endogenous neural mechanisms in the medial orbitofrontal cortex (mOFC) that regulate alcohol consumption.
- To investigate the role of specific neuronal ensembles in the mOFC in controlling binge drinking behavior.
Main Methods:
- Identification of a discrete GABAergic neuronal ensemble in the mOFC.
- Utilizing optogenetics to silence or ablate this neuronal population.
- Employing brain-wide analysis to trace neuronal projections.
- Investigating the recruitment of this ensemble by other rewarding substances.
Main Results:
- A specific GABAergic neuronal ensemble in the mOFC is recruited during alcohol intoxication and suppresses binge drinking.
- Silencing or ablating this mOFC neuronal ensemble leads to uncontrolled alcohol consumption.
- This neural ensemble is specific to alcohol and not activated by other rewarding substances.
- Projections from this mOFC ensemble to the mediodorsal thalamus are critical for regulating alcohol intake.
Conclusions:
- A novel brain circuit in the mOFC acts as a protective mechanism against binge alcohol drinking by halting intake.
- This finding provides crucial insights into the neurobiology of alcohol abuse.
- The identified mOFC neuronal ensemble represents a potential therapeutic target for interventions against alcohol use disorders.
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