Short-term field stimulation mimics synaptic maturation of hippocampal synapses
Short-term field stimulation mimics synaptic maturation of hippocampal synapses
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DOI：
10.1113/jphysiol.2011.224964
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发表时间：
2012-04-01
影响因子：
5.5
通讯作者：
Westbrook, Gary L.
中科院分区：
文献类型：
--
作者：
Bagley, Elena E.;Westbrook, Gary L.
突触传递的许多方面在发育过程中被修改，不仅反映了基因表达的发育程序的结果，而且还反映了正在进行的神经活动的影响。我们研究的作用，突触活动的成熟谢弗侧支（SC）-CA 1突触使用持续的低频场刺激急性脑切片。在出生后4-6天和14-16天之间，幼稚切片中的小鼠SC-CA 1突触显示出递质释放概率（P-r）的发育性降低和GluN 2A（NR 2A）亚基对NMDA受体介导的兴奋性突触后电流（EPSC）的贡献的增加。令人惊讶的是，这些发育变化可以模仿短期（4小时）在体外突触活动的切片从出生后（PND）4-6天的小鼠。然而，不同的活动水平需要改变释放概率相比，NMDA受体亚基组成。自发性突触活动足以改变NMDA受体亚基的组成，但持续的低频场刺激的脑切片（0.1 Hz，4小时）是必要的，以减少释放概率，评估1小时后停止刺激。蛋白质合成抑制剂茴香霉素阻断了场刺激对释放概率的影响。这些结果表明，成熟的兴奋性突触的功能可以在未成熟的神经元中迅速诱导。Pr和NMDA受体亚基组合物的活性依赖性充当先前神经活性的敏感指标，并提供兴奋性突触功效的稳态控制的双重机制。
Many aspects of synaptic transmission are modified during development, reflecting not only the consequence of developmental programmes of gene expression, but also the effects of ongoing neural activity. We investigated the role of synaptic activity in the maturation of Schaffer collateral (SC)-CA1 synapses using sustained low frequency field stimulation of acute brain slices. Between postnatal days 4-6 and 14-16, mouse SC-CA1 synapses in naive slices showed a developmental decrease in the probability of transmitter release (P-r) and an increase in the contribution of GluN2A (NR2A) subunits to the NMDA receptor-mediated excitatory postsynaptic current (EPSC). Surprisingly, these developmental changes could be mimicked by short term (4 h) in vitro synaptic activity in slices taken from postnatal days (PND) 4-6 mice. However, different activity levels were required to alter release probability compared to the NMDA receptor subunit composition. Spontaneous synaptic activity was sufficient to alter the NMDA receptor subunit composition, but sustained low-frequency field stimulation of the brain slice (0.1 Hz, 4 h) was necessary to reduce release probability, as assessed 1 h following the cessation of stimulation. The protein synthesis inhibitor anisomycin blocked the effect of field stimulation on release probability. These results indicate that features of mature excitatory synapses can be rapidly induced in immature neurons. The activity dependence of the Pr and NMDA receptor subunit composition serves as a sensitive indicator of prior neural activity, and provides dual mechanisms for homeostatic control of excitatory synaptic efficacy.