PMID- 16709674 OWN - NLM STAT- MEDLINE DCOM- 20060726 LR - 20181113 IS - 0027-8424 (Print) IS - 1091-6490 (Electronic) IS - 0027-8424 (Linking) VI - 103 IP - 22 DP - 2006 May 30 TI - Postsynaptic inositol 1,4,5-trisphosphate signaling maintains presynaptic function of parallel fiber-Purkinje cell synapses via BDNF. PG - 8528-33 AB - 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. FAU - Furutani, Kazuharu AU - Furutani K AD - Department of Pharmacology, Graduate School of Medicine, University of Tokyo, Tokyo 113-0033, Japan. FAU - Okubo, Yohei AU - Okubo Y FAU - Kakizawa, Sho AU - Kakizawa S FAU - Iino, Masamitsu AU - Iino M LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20060518 PL - United States TA - Proc Natl Acad Sci U S A JT - Proceedings of the National Academy of Sciences of the United States of America JID - 7505876 RN - 0 (Brain-Derived Neurotrophic Factor) RN - 0 (Receptors, Metabotropic Glutamate) RN - 0 (Receptors, N-Methyl-D-Aspartate) RN - 85166-31-0 (Inositol 1,4,5-Trisphosphate) RN - EC 3.1.3.- (inositol triphosphate phosphomonoesterase) RN - EC 3.1.3.2 (Phosphoric Monoester Hydrolases) SB - IM MH - Animals MH - Brain-Derived Neurotrophic Factor/*metabolism MH - Electrophysiology MH - Inositol 1,4,5-Trisphosphate/*metabolism MH - Mice MH - Mice, Inbred C57BL MH - Phosphoric Monoester Hydrolases/genetics/metabolism MH - Purkinje Cells/*metabolism MH - Receptors, Metabotropic Glutamate/metabolism MH - Receptors, N-Methyl-D-Aspartate/metabolism MH - *Signal Transduction MH - Synapses/*metabolism PMC - PMC1482525 COIS- Conflict of interest statement: No conflicts declared. EDAT- 2006/05/20 09:00 MHDA- 2006/07/27 09:00 PMCR- 2006/11/18 CRDT- 2006/05/20 09:00 PHST- 2006/05/20 09:00 [pubmed] PHST- 2006/07/27 09:00 [medline] PHST- 2006/05/20 09:00 [entrez] PHST- 2006/11/18 00:00 [pmc-release] AID - 0600497103 [pii] AID - 2355 [pii] AID - 10.1073/pnas.0600497103 [doi] PST - ppublish SO - Proc Natl Acad Sci U S A. 2006 May 30;103(22):8528-33. doi: 10.1073/pnas.0600497103. Epub 2006 May 18.