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.
Highlights
Synaptic plasticity is a modification of synaptic strength, which is important to the formation and stability of neuronal circuits
Our present results indicate that sensory stimulation induces an eCBdependent long-term depression (LTD) of GABAergic transmission at molecular interneurons (MLI)–Purkinje cells (PC) synapses via NMDA receptor activation in living animals
Repeated Facial Stimulation Induces LTD of GABAergic Transmission at MLI–PC Synapses In Vivo in Mice MLI–PC synaptic plasticity induced by postsynaptic depolarization at SC–PC synapses under in vitro conditions involves presynaptic cannabinoid type 1 (CB1) receptors (Llano et al, 1991a; Yoshida et al, 2002), NMDA receptors (Duguid and Smart, 2004), and postsynaptic GABAA receptors (Hirano and Kawaguchi, 2014)
Summary
Synaptic plasticity is a modification of synaptic strength, which is important to the formation and stability of neuronal circuits. Repetitive stimulation of CFs can induce GABAergic transmission LTP in PCs (Kano et al, 1996; Kawaguchi and Hirano, 2002). The increased Ca2+ transient activates calmodulindependent protein kinase II (CaMKII), which in turn regulates GABAergic transmission at MLI–PC synapses via GABAA receptors (Kano et al, 1992, 1996; Kawaguchi and Hirano, 2007). Similar to the synaptic plasticity at PF–PC, PF–MLI, and MF–GC synapses, MLI–PC synaptic plasticity may be related to cerebellar motor learning (Hirano and Kawaguchi, 2014). MLI–PC GABAergic LTD was not blocked by an mGluR1 antagonist, but was abolished by blockade of NMDA receptors during 1 Hz facial stimulation These results indicate that sensory stimulation induces an eCB-dependent LTD of GABAergic transmission at MLI–PC synapses via activation of NMDA receptors in vivo in mice
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