Intracellular Ca2+ stores and Ca2+ influx are both required for BDNF to rapidly increase quantal vesicular transmitter release.
Intracellular Ca2+ stores and Ca2+ influx are both required for BDNF to rapidly increase quantal vesicular transmitter release.
复制标题
DOI：
10.1155/2012/203536
复制
发表时间：
2012
影响因子：
3.1
通讯作者：
Pozzo-Miller L
中科院分区：
文献类型：
--
作者：
Amaral MD;Pozzo-Miller L
脑源性神经营养因子(BDNF)是脑发育过程中的生存因子，也是成人突触可塑性的调节因子。启动BDNF作用的一个潜在机制是通过它对量子突触前递质释放的调节。在CA1区锥体神经元局部应用脑源性神经营养因子后，30s内微小兴奋性突触后电流(MEPSC)的频率显著增加，mEPSC的幅度和动力学无明显变化。这种作用是通过激活TrkB受体来实现的，需要细胞内和细胞外的全部钙离子储备。与TRPC家族的钙离子通透性质膜通道的作用一致，抑制剂SKF96365阻止了BDNF诱导的mEPSC频率的增加。此外，用两亲性的苯乙酰染料标记突触前终末，然后用多光子激发显微镜监测它们在脑片培养中的BDNF染色后发现，mEPSCs频率的增加反映了囊泡融合事件。事实上，将BDNF应用于TTX中CA3-CA1突触，迅速增加了FM1-43或FM2-10的染色，其时间过程与mEPSC频率增加的时相平行。我们得出结论，BDNF通过一种涉及TrkB受体、钙库和TRPC通道的突触前钙依赖机制促进囊泡融合，从而增加mEPSC的频率。
Brain-derived neurotrophic factor (BDNF) is well known as a survival factor during brain development as well as a regulator of adult synaptic plasticity. One potential mechanism to initiate BDNF actions is through its modulation of quantal presynaptic transmitter release. In response to local BDNF application to CA1 pyramidal neurons, the frequency of miniature excitatory postsynaptic currents (mEPSC) increased significantly within 30 seconds; mEPSC amplitude and kinetics were unchanged. This effect was mediated via TrkB receptor activation and required both full intracellular Ca2+ stores as well as extracellular Ca2+. Consistent with a role of Ca2+-permeable plasma membrane channels of the TRPC family, the inhibitor SKF96365 prevented the BDNF-induced increase in mEPSC frequency. Furthermore, labeling presynaptic terminals with amphipathic styryl dyes and then monitoring their post-BDNF destaining in slice cultures by multiphoton excitation microscopy revealed that the increase in frequency of mEPSCs reflects vesicular fusion events. Indeed, BDNF application to CA3-CA1 synapses in TTX rapidly enhanced FM1-43 or FM2-10 destaining with a time course that paralleled the phase of increased mEPSC frequency. We conclude that BDNF increases mEPSC frequency by boosting vesicular fusion through a presynaptic, Ca2+-dependent mechanism involving TrkB receptors, Ca2+ stores, and TRPC channels.
登录
查看更多内容
影响因子：
5.3
作者：
Carter, AG;Vogt, KE;Regehr, WG
通讯作者：
Regehr, WG
影响因子：
5.7
作者：
Axmacher, N;Winterer, J;Müller, W
通讯作者：
Müller, W
影响因子：
2
作者：
Alonso, M;Medina, JH;Pozzo-Miller, L
通讯作者：
Pozzo-Miller, L
影响因子：
5.3
作者：
Amaral, Michelle D.;Pozzo-Miller, Lucas
通讯作者：
Pozzo-Miller, Lucas
影响因子：
16.2
作者：
Emptage, NJ;Reid, CA;Fine, A
通讯作者：
Fine, A