title: Facial stimulation induces long-term depression at cerebellar molecular layer interneuron-Purkinje cell synapses in vivo in mice.
abstract: Cerebellar long-term synaptic plasticity has been proposed to provide a cellular mechanism for motor learning. Numerous studies have demonstrated the induction and mechanisms of synaptic plasticity at parallel fiber-Purkinje cell (PF-PC), parallel fiber-molecular layer interneurons (PF-MLI) and mossy fiber-granule cell (MF-GC) synapses, but no study has investigated sensory stimulation-evoked synaptic plasticity at MLI-PC synapses in the cerebellar cortex of living animals. We studied the expression and mechanism of MLI-PC GABAergic synaptic plasticity induced by a train of facial stimulation in urethane-anesthetized mice by cell-attached recordings and pharmacological methods. We found that 1 Hz, but not a 2 Hz or 4 Hz, facial stimulation induced a long-term depression (LTD) of GABAergic transmission at MLI-PC synapses, which was accompanied with a decrease in the stimulation-evoked pause of spike firing in PCs, but did not induce a significant change in the properties of the sensory-evoked spike events of MLIs. The MLI-PC GABAergic LTD could be prevented by blocking cannabinoid type 1 (CB1) receptors, and could be pharmacologically induced by a CB1 receptor agonist. Additionally, 1 Hz facial stimulation delivered in the presence of a metabotropic glutamate receptor 1 (mGluR1) antagonist, JNJ16259685, still induced the MLI-PC GABAergic LTD, whereas blocking N-methyl-D-aspartate (NMDA) receptors during 1 Hz facial stimulation abolished the expression of MLI-PC GABAergic LTD. These results indicate that sensory stimulation can induce an endocannabinoid (eCB)-dependent LTD of GABAergic transmission at MLI-PC synapses via activation of NMDA receptors in cerebellar cortical Crus II in vivo in mice. Our results suggest that the sensory stimulation-evoked MLI-PC GABAergic synaptic plasticity may play a critical role in motor learning in animals.
authors.affiliation: Cellular Function Research Center, Yanbian University Yanji, Jilin Province, China ; Department of Physiology and Pathophysiology, College of Medicine, Yanbian University Yanji, Jilin Province, China.
authors.forename: Yan-Hua
authors.initials: YH
authors.lastname: Bing
authors.affiliation: Cellular Function Research Center, Yanbian University Yanji, Jilin Province, China ; Department of Osteology, Affiliated Hospital of Yanbian University Yanji, Jilin Province, China.
authors.forename: Mao-Cheng
authors.initials: MC
authors.lastname: Wu
authors.affiliation: Cellular Function Research Center, Yanbian University Yanji, Jilin Province, China.
authors.forename: Chun-Ping
authors.initials: CP
authors.lastname: Chu
authors.affiliation: Cellular Function Research Center, Yanbian University Yanji, Jilin Province, China ; Department of Physiology and Pathophysiology, College of Medicine, Yanbian University Yanji, Jilin Province, China.
authors.forename: De-Lai
authors.initials: DL
authors.lastname: Qiu
keywords: NMDA receptor; cerebellar Purkinje cell; endocannabinoids receptor; in vivo cell-attached recording; molecular layer interneuron; plasticity; sensory stimulation