Bouabid Safa, Zhang Liangzhu, T Vu Mai-Anh, Tang Kylie, Graham Benjamin M, Noggle Christian A, Howe Mark W
Department of Psychological & Brain Sciences, Boston University, Boston, MA, USA.
Aligning Science Across Parkinson's (ASAP) Collaborative Research Network, Chevy Chase, MD, USA.
Nat Commun. 2025 Jun 4;16(1):5169. doi: 10.1038/s41467-025-60462-5.
Striatal acetylcholine (ACh) signaling is thought to counteract reinforcement signals, promoting extinction and behavioral flexibility. Changes in striatal ACh signals have been reported during learning, but how ACh signals for learning and extinction are spatially organized to enable region-specific plasticity is unclear. We used array photometry in mice to reveal a topography of opposing changes in ACh release across distinct striatal regions. Reward prediction error encoding was localized to specific phases of ACh dynamics in anterior dorsal striatum (aDS): positive and negative prediction errors were expressed in dips and elevations respectively. Silencing ACh release in aDS impaired extinction, suggesting a role for ACh elevations in down-regulating cue-reward associations. Dopamine release in aDS dipped for cues during extinction, inverse to ACh, while glutamate input onto cholinergic interneurons was unchanged. These findings pinpoint where and suggest an intrastriatal mechanism for how ACh dynamics shape region-specific plasticity to gate learning and promote extinction.
纹状体乙酰胆碱（ACh）信号被认为可抵消强化信号，促进消退和行为灵活性。已有研究报道在学习过程中纹状体ACh信号会发生变化，但尚不清楚用于学习和消退的ACh信号是如何在空间上组织起来以实现区域特异性可塑性的。我们利用小鼠的阵列光度法揭示了不同纹状体区域ACh释放的相反变化的拓扑结构。奖励预测误差编码定位于前背侧纹状体（aDS）中ACh动态变化的特定阶段：正向和负向预测误差分别在下降和上升阶段表现出来。抑制aDS中的ACh释放会损害消退，表明ACh升高在下调线索-奖励关联中起作用。在消退过程中，aDS中的多巴胺释放对于线索会下降，与ACh相反，而胆碱能中间神经元上的谷氨酸输入则保持不变。这些发现明确了位置，并提出了一种纹状体内机制，即ACh动态变化如何塑造区域特异性可塑性以控制学习并促进消退。
