Department of Neurology, University of California, San Francisco, CA 94158.
Department of Psychiatry and Behavioral Science, University of California, San Francisco, CA 94107.
Proc Natl Acad Sci U S A. 2024 Oct 8;121(41):e2410828121. doi: 10.1073/pnas.2410828121. Epub 2024 Oct 4.
Striatal acetylcholine and dopamine critically regulate movement, motivation, and reward-related learning. Pauses in cholinergic interneuron (CIN) firing are thought to coincide with dopamine pulses encoding reward prediction errors (RPE) to jointly enable synaptic plasticity. Here, we examine the firing of identified CINs during reward-guided decision-making in freely moving rats and compare this firing to dopamine release. Relationships between CINs, dopamine, and behavior varied strongly by subregion. In the dorsal-lateral striatum, a cue evoked burst-pause CIN spiking, followed by a brief dopamine pulse that was unrelated to RPE. In the dorsal-medial striatum, this cue evoked only a CIN pause, that was curtailed by a movement-selective rebound in firing. Finally, in the ventral striatum, a reward cue evoked RPE-coding increases in both dopamine and CIN firing, without a consistent pause. Our results demonstrate a spatial and temporal dissociation between CIN pauses and dopamine RPE signals and will inform future models of striatal information processing under both normal and pathological conditions.
纹状体中的乙酰胆碱和多巴胺对运动、动机和奖赏相关学习起着关键的调节作用。人们认为，胆碱能中间神经元（CIN）放电的暂停与编码奖赏预测误差（RPE）的多巴胺脉冲同时发生，从而共同实现突触可塑性。在这里，我们在自由活动的大鼠中检查了在奖赏指导的决策过程中被识别的 CIN 的放电情况，并将其与多巴胺的释放进行了比较。CIN、多巴胺和行为之间的关系在各个亚区之间存在很大差异。在背外侧纹状体中，一个线索引发了 CIN 的爆发-暂停放电，随后是一个与 RPE 无关的短暂多巴胺脉冲。在背内侧纹状体中，这个线索只引发了 CIN 的暂停，随后是由运动选择引起的放电反弹。最后，在腹侧纹状体中，一个奖赏线索引发了多巴胺和 CIN 放电的 RPE 编码增加，而没有一致的暂停。我们的结果表明，CIN 暂停和多巴胺 RPE 信号之间存在空间和时间上的分离，这将为正常和病理条件下纹状体信息处理的未来模型提供信息。
