Laboratory of Sensory Processing, Brain Mind Institute, Faculty of Life Sciences, Ecole Polytechnique Fédérale de Lausanne (EPFL), Lausanne, CH-1015, Switzerland.
Department of Psychiatry and Physiology and Neuroscience, New York University Langone Medical Center, New York, NY 10016, USA.
Function (Oxf). 2021 Sep 21;2(6):zqab049. doi: 10.1093/function/zqab049. eCollection 2021.
The striatum integrates sensorimotor and motivational signals, likely playing a key role in reward-based learning of goal-directed behavior. However, cell type-specific mechanisms underlying reinforcement learning remain to be precisely determined. Here, we investigated changes in membrane potential dynamics of dorsolateral striatal neurons comparing naïve mice and expert mice trained to lick a reward spout in response to whisker deflection. We recorded from three distinct cell types: (i) direct pathway striatonigral neurons, which express type 1 dopamine receptors; (ii) indirect pathway striatopallidal neurons, which express type 2 dopamine receptors; and (iii) tonically active, putative cholinergic, striatal neurons. Task learning was accompanied by cell type-specific changes in the membrane potential dynamics evoked by the whisker deflection and licking in successfully-performed trials. Both striatonigral and striatopallidal types of striatal projection neurons showed enhanced task-related depolarization across learning. Striatonigral neurons showed a prominent increase in a short latency sensory-evoked depolarization in expert compared to naïve mice. In contrast, the putative cholinergic striatal neurons developed a hyperpolarizing response across learning, driving a pause in their firing. Our results reveal cell type-specific changes in striatal membrane potential dynamics across the learning of a simple goal-directed sensorimotor transformation, helpful for furthering the understanding of the various potential roles of different basal ganglia circuits.
纹状体整合感觉运动和动机信号，可能在基于奖励的目标导向行为学习中发挥关键作用。然而，强化学习背后的细胞类型特异性机制仍有待精确确定。在这里，我们比较了未训练的小鼠和经过训练以响应胡须偏转舔取奖励喷口的专家小鼠，研究了背外侧纹状体神经元膜电位动力学的变化。我们从三种不同的细胞类型进行了记录：（i）直接通路纹状体苍白球神经元，表达 1 型多巴胺受体；（ii）间接通路纹状体黑质神经元，表达 2 型多巴胺受体；以及（iii）持续活动的、假定的胆碱能纹状体神经元。任务学习伴随着在成功执行的试验中由胡须偏转和舔舐引起的膜电位动力学的细胞类型特异性变化。两种纹状体投射神经元，纹状体苍白球神经元和纹状体黑质神经元，在整个学习过程中都表现出与任务相关的去极化增强。与未训练的小鼠相比，纹状体苍白球神经元在专家小鼠中表现出明显的短潜伏期感觉诱发去极化增加。相比之下，假定的胆碱能纹状体神经元在整个学习过程中表现出超极化反应，驱动其放电暂停。我们的结果揭示了在简单的目标导向感觉运动转换学习过程中纹状体膜电位动力学的细胞类型特异性变化，有助于进一步了解不同基底神经节回路的各种潜在作用。
