Postsynaptic inositol 1,4,5-trisphosphate signaling maintains presynaptic function of parallel fiber-Purkinje cell synapses via BDNF.
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.
Furutani
Kazuharu
K
Department of Pharmacology, Graduate School of Medicine, University of Tokyo, Tokyo 113-0033, Japan.
Okubo
Yohei
Y
Kakizawa
Sho
S
Iino
Masamitsu
M
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*
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