title: Postsynaptic inositol 1,4,5-trisphosphate signaling maintains presynaptic function of parallel fiber-Purkinje cell synapses via BDNF.
abstract: The maintenance of synaptic functions is essential for neuronal information processing, but cellular mechanisms that maintain synapses in the adult brain are not well understood. Here, we report an activity-dependent maintenance mechanism of parallel fiber (PF)-Purkinje cell (PC) synapses in the cerebellum. When postsynaptic metabotropic glutamate receptor (mGluR) or inositol 1,4,5-trisphosphate (IP(3)) signaling was chronically inhibited in vivo, PF-PC synaptic strength decreased because of a decreased transmitter release probability. The same effects were observed when PF activity was inhibited in vivo by the suppression of NMDA receptor-mediated inputs to granule cells. PF-PC synaptic strength similarly decreased after the in vivo application of an antibody against brain-derived neurotrophic factor (BDNF). Furthermore, the weakening of synaptic connection caused by the blockade of mGluR-IP(3) signaling was reversed by the in vivo application of BDNF. These results indicate that a signaling cascade comprising PF activity, postsynaptic mGluR-IP(3) signaling and subsequent BDNF signaling maintains presynaptic functions in the mature cerebellum.
authors.affiliation: Department of Pharmacology, Graduate School of Medicine, University of Tokyo, Tokyo 113-0033, Japan.
authors.forename: Kazuharu
authors.initials: K
authors.lastname: Furutani
authors.forename: Yohei
authors.initials: Y
authors.lastname: Okubo
authors.forename: Sho
authors.initials: S
authors.lastname: Kakizawa
authors.forename: Masamitsu
authors.initials: M
authors.lastname: Iino
mesh_terms: D000818:Animals; D019208:Brain-Derived Neurotrophic Factor / Q000378:metabolism*; D004594:Electrophysiology; D015544:Inositol 1,4,5-Trisphosphate / Q000378:metabolism*; D051379:Mice; D008810:Mice, Inbred C57BL; D010744:Phosphoric Monoester Hydrolases / Q000235:genetics / Q000378:metabolism; D011689:Purkinje Cells / Q000378:metabolism*; D018094:Receptors, Metabotropic Glutamate / Q000378:metabolism; D016194:Receptors, N-Methyl-D-Aspartate / Q000378:metabolism; D015398:Signal Transduction; D013569:Synapses / Q000378:metabolism*
chemical_list: D019208:Brain-Derived Neurotrophic Factor; D018094:Receptors, Metabotropic Glutamate; D016194:Receptors, N-Methyl-D-Aspartate; D015544:Inositol 1,4,5-Trisphosphate; C035215:inositol triphosphate phosphomonoesterase; D010744:Phosphoric Monoester Hydrolases