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Mixed representations of choice direction and outcome by GABA/glutamate cotransmitting neurons in the entopeduncular nucleus.

Julianna Locantore | Yijun Liu | Jesse White | Janet Berrios Wallace | Celia Beron | Emily Kraft | Bernardo Sabatini | Michael Wallace
eLife | 2025

The basal ganglia (BG) are an evolutionarily conserved and phylogenetically old set of sub-cortical nuclei that guide action selection, evaluation, and reinforcement. The entopeduncular nucleus (EP) is a major BG output nucleus that contains a population of GABA/glutamate cotransmitting neurons (EPSst+) that specifically target the lateral habenula (LHb) and whose function in behavior remains mysterious. Here, we use a probabilistic switching task that requires an animal to maintain flexible relationships between action selection and evaluation to examine when and how GABA/glutamate cotransmitting neurons contribute to behavior. We find that EPSst+ neurons are strongly engaged during this task and show bidirectional changes in activity during the choice and outcome periods of a trial. We then tested the effects of either permanently blocking cotransmission or modifying the GABA/glutamate ratio on behavior in well-trained animals. Neither manipulation produced detectable changes in behavior despite significant changes in synaptic transmission in the LHb, demonstrating that the outputs of these neurons are not required for ongoing action-outcome updating in a probabilistic switching task.

Pubmed ID: 39835778

Associated grants

  • Agency: NIMH NIH HHS, United States
    Id: R01 MH133608
  • Agency: NINDS NIH HHS, United States
    Id: R00NS105883
  • Agency: NINDS NIH HHS, United States
    Id: R01NS103226
  • Agency: NIMH NIH HHS, United States
    Id: R01MH133608
  • Agency: NINDS NIH HHS, United States
    Id: R00 NS105883
  • Agency: NINDS NIH HHS, United States
    Id: R01 NS103226

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