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bioRxiv · 10.1101/2024.06.07.597980

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

Locantore, J.·White, J.·Wallace, J. B.·Beron, C. C.·Sabatini, B. L.·Wallace, M. L.
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Abstract

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 on-going action-outcome updating in a probabilistic switching task.

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Locantore, J., White, J., Wallace, J. B., Beron, C. C., Sabatini, B. L., Wallace, M. L.. 2024-06-08. Mixed representations of choice and outcome by GABA/glutamate cotransmitting neurons in the entopeduncular nucleus. https://doi.org/10.1101/2024.06.07.597980

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