Postsynaptic inositol 1,4,5-trisphosphate signaling maintains presynaptic function of parallel fiber-Purkinje cell synapses via BDNF
Postsynaptic inositol 1,4,5-trisphosphate signaling maintains presynaptic function of parallel fiber-Purkinje cell synapses via BDNF
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DOI：
10.1073/pnas.0600497103
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发表时间：
2006-05-30
影响因子：
11.1
通讯作者：
Iino, Masamitsu
中科院分区：
文献类型：
--
作者：
Furutani, Kazuharu;Okubo, Yohei;Iino, Masamitsu
突触功能的维持对神经元信息处理至关重要，但维持成人大脑突触的细胞机制尚不清楚。在这里，我们报道了小脑平行纤维(PF)-浦肯野细胞（PC）突触的活动依赖维持机制。当体内代谢后谷氨酸受体（mGluR）或肌醇1,4,5-三磷酸（IP3）信号被长期抑制时，由于递质释放概率降低，PF-PC突触强度下降。当通过抑制NMDA受体介导的颗粒细胞输入来抑制体内PF活性时，观察到同样的效果。在体内应用抗脑源性神经营养因子（BDNF）抗体后，PF-PC突触强度也同样下降。此外，体内应用BDNF可逆转mGluR-IP3信号通路阻断导致的突触连接减弱。这些结果表明，由PF活性、突触后mGluR-IP3信号和随后的BDNF信号组成的信号级联维持了成熟小脑的突触前功能。
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.