Lee Ka Hung, Mathews Paul J, Reeves Alexander M B, Choe Katrina Y, Jami Shekib A, Serrano Raul E, Otis Thomas S
Department of Neurobiology and Integrated Center for Learning and Memory, Geffen School of Medicine at UCLA, 650 Charles E. Young Drive, Los Angeles, CA 90095, USA.
Department of Neurobiology and Integrated Center for Learning and Memory, Geffen School of Medicine at UCLA, 650 Charles E. Young Drive, Los Angeles, CA 90095, USA; Interdepartmental Program in Neuroscience, Geffen School of Medicine at UCLA, 650 Charles E. Young Drive, Los Angeles, CA 90095, USA.
Neuron. 2015 Apr 22;86(2):529-40. doi: 10.1016/j.neuron.2015.03.010. Epub 2015 Apr 2.
The cerebellum stores associative motor memories essential for properly timed movement; however, the mechanisms by which these memories form and are acted upon remain unclear. To determine how cerebellar activity relates to movement and motor learning, we used optogenetics to manipulate spontaneously firing Purkinje neurons (PNs) in mouse simplex lobe. Using high-speed videography and motion tracking, we found that altering PN activity produced rapid forelimb movement. PN inhibition drove movements time-locked to stimulus onset, whereas PN excitation drove delayed movements time-locked to stimulus offset. Pairing either PN inhibition or excitation with sensory stimuli triggered the formation of robust, associative motor memories; however, PN excitation led to learned movements whose timing more closely matched training intervals. These findings implicate inhibition of PNs as a teaching signal, consistent with a model whereby learning leads first to reductions in PN firing that subsequently instruct circuit changes in the cerebellar nucleus.
小脑存储对运动时机恰当至关重要的联合运动记忆;然而,这些记忆形成及发挥作用的机制仍不清楚。为了确定小脑活动与运动及运动学习之间的关系,我们使用光遗传学方法操纵小鼠单小叶中自发放电的浦肯野神经元(PNs)。通过高速摄像和运动跟踪,我们发现改变PN活动会产生快速的前肢运动。PN抑制驱动与刺激开始时间锁定的运动,而PN兴奋驱动与刺激结束时间锁定的延迟运动。将PN抑制或兴奋与感觉刺激配对会触发强大的联合运动记忆的形成;然而,PN兴奋导致习得的运动,其时间更紧密地匹配训练间隔。这些发现表明PN的抑制是一种教学信号,这与一种模型一致,即学习首先导致PN放电减少,随后指导小脑核中的电路变化。