Program in Neuroscience & Mental Health, Lee Kong Chian School of Medicine, Nanyang Technological University, Singapore, Singapore; Institute of Molecular and Cell Biology, Singapore, Singapore
Andrei Khilkevich
Center for Learning and Memory, The University of Texas, Austin, United States
Michael D Mauk
Center for Learning and Memory, The University of Texas, Austin, United States; Department of Neuroscience, The University of Texas, Austin, United States
Program in Neuroscience & Mental Health, Lee Kong Chian School of Medicine, Nanyang Technological University, Singapore, Singapore; Institute of Molecular and Cell Biology, Singapore, Singapore
The function of a feedback inhibitory circuit between cerebellar Purkinje cells and molecular layer interneurons (MLIs) was defined by combining optogenetics, neuronal activity recordings both in cerebellar slices and in vivo, and computational modeling. Purkinje cells inhibit a subset of MLIs in the inner third of the molecular layer. This inhibition is non-reciprocal, short-range (less than 200 μm) and is based on convergence of one to two Purkinje cells onto MLIs. During learning-related eyelid movements in vivo, the activity of a subset of MLIs progressively increases as Purkinje cell activity decreases, with Purkinje cells usually leading the MLIs. Computer simulations indicate that these relationships are best explained by the feedback circuit from Purkinje cells to MLIs and that this feedback circuit plays a central role in making cerebellar learning efficient.