TY - JOUR
T1 - Postsynaptic inositol 1,4,5-triphosphate signaling maintains presynaptic function of parallel fiber-Purkinje cell synapses via BDNF
AU - Furutani, Kazuharu
AU - Okubo, Yohei
AU - Kakizawa, Sho
AU - Iino, Masamitsu
PY - 2006/5/30
Y1 - 2006/5/30
N2 - 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 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-IP3 signaling was reversed by the in 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.
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 (IP3) 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-IP3 signaling was reversed by the in 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.
KW - Adult mouse
KW - Cerebellum
KW - Metabotropic glutamate receptor
KW - Neuronal activity
KW - Retrograde signaling
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U2 - 10.1073/pnas.0600497103
DO - 10.1073/pnas.0600497103
M3 - Article
C2 - 16709674
AN - SCOPUS:33744809837
VL - 103
SP - 8528
EP - 8533
JO - Proceedings of the National Academy of Sciences of the United States of America
JF - Proceedings of the National Academy of Sciences of the United States of America
SN - 0027-8424
IS - 22
ER -