Table of Contents
- 1 Comment; The ventro-medial pre-frontal cortex is a key region of the brain involved in alcohol use disorder in mice. This can probably be extrapolated to humans, giving us another specific area of the brain to target as a clue for for development of new treatments for alcohol addiction.
- 2 Article Info
- 3 Article Outline
- 4 Abstract
Comment; The ventro-medial pre-frontal cortex is a key region of the brain involved in alcohol use disorder in mice. This can probably be extrapolated to humans, giving us another specific area of the brain to target as a clue for for development of new treatments for alcohol addiction.
Lindsay R. Halladay1,2,∗,Correspondence information about the author Lindsay R. HalladayEmail the author Lindsay R. Halladay, Adrina Kocharian1, Patrick T. Piantadosi1,5, Michael E. Authement3,5, Abby G. Lieberman1, Nathen A. Spitz1, Kendall Coden1, Lucas R. Glover1, Vincent D. Costa4, Veronica A. Alvarez3,5, Andrew Holmes1Open AccessPlumX MetricsDOI: https://doi.org/10.1016/j.biopsych.2019.10.030
Audio/VideoDownload File (3.02 MB)behavior_leverabort.wmv
- Methods and Materials
- Punishment suppresses EtOH-SA
- Neuronal correlates of punished EtOH-SA
- vmPFC-coding punished of EtOH-SA
- Silencing vmPFC abolishes punished-suppression of EtOH-SA
- dmPFC-coding of punished EtOH-SA
- dmPFC-photosilencing does not affect punished-suppression of EtOH-SA
- Punished-suppression of EtOH-SA produces vmPFC→NAc plasticity
- Silencing vmPFC→NAcS, not vmPFC→BLA, attenuates punished-suppression of EtOH-SA
- Minimal collateralization of vmPFC neurons to NAcS and BA
- Financial Disclosures
- Appendix A. Supplementary data
Jump to SectionIntroductionMethods and Materials Subjects Ethical considerations Behavioral testing In vivo neuronal recordings Fluorescence in situ hybridization (FISH) Ex vivo whole-cell recordings In vivo photosilencing Retrograde neuronal tracing Statistical analysisResults Punishment suppresses EtOH-SA Neuronal correlates of punished EtOH-SA vmPFC-coding punished of EtOH-SA Silencing vmPFC abolishes punished-suppression of EtOH-SA dmPFC-coding of punished EtOH-SA dmPFC-photosilencing does not affect punished-suppression of EtOH-SA Punished-suppression of EtOH-SA produces vmPFC→NAc plasticity Silencing vmPFC→NAcS, not vmPFC→BLA, attenuates punished-suppression of EtOH-SA Minimal collateralization of vmPFC neurons to NAcS and BADiscussionFinancial DisclosuresAppendix A. Supplementary dataReferences
A clinical hallmark of alcohol use disorder (AUD) is persistent drinking despite potential adverse consequences. The ventral (vmPFC) and dorsal (dmPFC) medial prefrontal cortex are positioned to exert top-down control over subcortical regions, such as the nucleus accumbens shell (NAcS) and basolateral amygdala (BLA), which encode positive and negative valence of EtOH-related stimuli. Prior rodent studies have implicated these regions in regulation of punished EtOH self-administration (EtOH-SA).
We conducted in vivo electrophysiological recordings in mouse vmPFC and dmPFC to obtain neuronal correlates of footshock-punished EtOH-SA. Ex vivo recordings were performed in NAcS D1-positive MSNs receiving vmPFC input to examine punishment-related plasticity in this pathway. Optogenetic photosilencing was employed to assess the functional contribution of the vmPFC and dmPFC, vmPFC projections to NAcS or BLA, to punished EtOH-SA.
Punishment reduced EtOH-lever pressing and elicited aborted presses (lever approach followed by rapid retraction). Neurons in vmPFC and dmPFC exhibited phasic firing to EtOH-lever presses and aborts, but only in vmPFC was there a population-level shift in coding from lever presses to aborts with punishment. Closed-loop vmPFC, not dmPFC, photosilencing on a post-punishment probe test negated the reduction in EtOH-lever presses but not aborts. Punishment was associated with altered plasticity at vmPFC inputs to D1-MSNs in NAcS. Photosilencing vmPFC projections to NAcS, not BLA, partially reversed suppression of EtOH-lever presses on probe testing.
These findings demonstrate a key role for vmPFC in regulating EtOH-SA after punishment, with implications for understanding the neural basis of compulsive drinking in AUDs.
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