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. HalladayAdrina Kocharian1Patrick T. Piantadosi1,5Michael E. Authement3,5Abby G. Lieberman1Nathen A. Spitz1Kendall Coden1Lucas R. Glover1Vincent D. Costa4Veronica A. Alvarez3,5Andrew Holmes1Open AccessPlumX MetricsDOI:

Article Info

Audio/VideoDownload File (3.02 MB)behavior_leverabort.wmv

Article Outline

  1. Introduction
  2. Methods and Materials
    1. Subjects
    2. Ethical considerations
    3. Behavioral testing
    4. In vivo neuronal recordings
    5. Fluorescence in situ hybridization (FISH)
    6. Ex vivo whole-cell recordings
    7. In vivo photosilencing
    8. Retrograde neuronal tracing
    9. Statistical analysis
  3. Results
    1. Punishment suppresses EtOH-SA
    2. Neuronal correlates of punished EtOH-SA
    3. vmPFC-coding punished of EtOH-SA
    4. Silencing vmPFC abolishes punished-suppression of EtOH-SA
    5. dmPFC-coding of punished EtOH-SA
    6. dmPFC-photosilencing does not affect punished-suppression of EtOH-SA
    7. Punished-suppression of EtOH-SA produces vmPFC→NAc plasticity
    8. Silencing vmPFC→NAcS, not vmPFC→BLA, attenuates punished-suppression of EtOH-SA
    9. Minimal collateralization of vmPFC neurons to NAcS and BA
  4. Discussion
  5. Financial Disclosures
  6. Appendix A. Supplementary data
  7. References

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.

Dr. Raymond Oenbrink