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内苍白球中γ-氨基丁酸/谷氨酸共传递神经元对选择方向和结果的混合表征。

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

作者信息

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

机构信息

Department of Anatomy and Neurobiology, Boston University Chobanian & Avedisian School of Medicine, Boston, United States.

Howard Hughes Medical Institute, Department of Neurobiology, Harvard Medical School, Boston, United States.

出版信息

Elife. 2025 Jan 21;13:RP100488. doi: 10.7554/eLife.100488.

DOI:10.7554/eLife.100488
PMID:39835778
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC11750137/
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 (EP) 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 EP 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.

摘要

基底神经节（BG）是一组进化上保守且系统发育古老的皮质下核团，其指导动作选择、评估和强化。内苍白球核（EP）是基底神经节的一个主要输出核团，其中包含一群γ-氨基丁酸/谷氨酸共传递神经元（EP），这些神经元特异性地靶向外侧缰核（LHb），其在行为中的功能仍然未知。在这里，我们使用一种概率性切换任务，该任务要求动物在动作选择和评估之间保持灵活的关系，以研究γ-氨基丁酸/谷氨酸共传递神经元何时以及如何对行为产生影响。我们发现，在这项任务中EP神经元被强烈激活，并且在试验的选择和结果阶段其活动表现出双向变化。然后，我们测试了永久阻断共传递或改变γ-氨基丁酸/谷氨酸比例对训练有素的动物行为的影响。尽管LHb中的突触传递发生了显著变化，但这两种操作均未在行为上产生可检测到的变化，这表明在概率性切换任务中，正在进行的动作-结果更新不需要这些神经元的输出。

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