Open AccessPostsynaptic inositol 1,4,5-trisphosphate signaling maintains presynaptic function of parallel fiber–Purkinje cell synapses via BDNF
Author(s) -
Kazuharu Furutani,
Yohei Okubo,
Sho Kakizawa,
Masamitsu Iino
Publication year - 2006
Publication title -
proceedings of the national academy of sciences of the united states of america
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 5.011
H-Index - 771
eISSN - 1091-6490
pISSN - 0027-8424
DOI - 10.1073/pnas.0600497103
Subject(s) - metabotropic glutamate receptor , postsynaptic potential , parallel fiber , postsynaptic density , neuroscience , brain derived neurotrophic factor , purkinje cell , biology , microbiology and biotechnology , metabotropic glutamate receptor 1 , cerebellum , chemistry , excitatory postsynaptic potential , glutamate receptor , neurotrophic factors , inhibitory postsynaptic potential , receptor , biochemistry
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 (IP3 ) signaling was chronically inhibitedin vivo , PF–PC synaptic strength decreased because of a decreased transmitter release probability. The same effects were observed when PF activity was inhibitedin vivo by the suppression of NMDA receptor-mediated inputs to granule cells. PF–PC synaptic strength similarly decreased after thein vivo application of an antibody against brain-derived neurotrophic factor (BDNF). Furthermore, the weakening of synaptic connection caused by the blockade of mGluR–IP3 signaling was reversed by thein vivo application of BDNF. These results indicate that a signaling cascade comprising PF activity, postsynaptic mGluR–IP3 signaling and subsequent BDNF signaling maintains presynaptic functions in the mature cerebellum.