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 (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.
| Original language | English (US) |
|---|---|
| Pages (from-to) | 8528-8533 |
| Number of pages | 6 |
| Journal | Proceedings of the National Academy of Sciences of the United States of America |
| Volume | 103 |
| Issue number | 22 |
| DOIs | |
| State | Published - May 30 2006 |
| Externally published | Yes |
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Keywords
- Adult mouse
- Cerebellum
- Metabotropic glutamate receptor
- Neuronal activity
- Retrograde signaling
ASJC Scopus subject areas
- General
Cite this
Postsynaptic inositol 1,4,5-triphosphate signaling maintains presynaptic function of parallel fiber-Purkinje cell synapses via BDNF. / Furutani, Kazuharu; Okubo, Yohei; Kakizawa, Sho; Iino, Masamitsu.
In: Proceedings of the National Academy of Sciences of the United States of America, Vol. 103, No. 22, 30.05.2006, p. 8528-8533.Research output: Contribution to journal › Article
}
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
UR - http://www.scopus.com/inward/record.url?scp=33744809837&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=33744809837&partnerID=8YFLogxK
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 -