title: Circuit mechanisms underlying motor memory formation in the cerebellum.
abstract: 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.
authors.affiliation: 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.
authors.forename: Ka Hung
authors.initials: KH
authors.lastname: Lee
authors.affiliation: 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.
authors.forename: Paul J
authors.initials: PJ
authors.lastname: Mathews
authors.affiliation: 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.
authors.forename: Alexander M B
authors.initials: AM
authors.lastname: Reeves
authors.affiliation: 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.
authors.forename: Katrina Y
authors.initials: KY
authors.lastname: Choe
authors.affiliation: Department of Physiology, Geffen School of Medicine at UCLA, 650 Charles E. Young Drive, Los Angeles, CA 90095, USA.
authors.forename: Shekib A
authors.initials: SA
authors.lastname: Jami
authors.affiliation: Department of Physiology, Geffen School of Medicine at UCLA, 650 Charles E. Young Drive, Los Angeles, CA 90095, USA.
authors.forename: Raul E
authors.initials: RE
authors.lastname: Serrano
authors.affiliation: 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. Electronic address: otist@ucla.edu.
authors.forename: Thomas S
authors.initials: TS
authors.lastname: Otis
mesh_terms: D000818:Animals; D001245:Association Learning / Q000502:physiology*; D000075402:Channelrhodopsins; D005552:Forelimb / Q000502:physiology*; D066298:In Vitro Techniques; D051379:Mice; D008822:Mice, Transgenic; D009068:Movement / Q000502:physiology*; D009412:Nerve Fibers / Q000502:physiology; D009473:Neuronal Plasticity / Q000502:physiology*; D011689:Purkinje Cells / Q000502:physiology*; D065852:Spatial Memory / Q000502:physiology*
chemical_list: D000075402:Channelrhodopsins
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