Dendritic NMDA spikes are necessary for timing-dependent associative LTP in CA3 pyramidal cells.

Dendritic NMDA spikes are necessary for timing-dependent associative LTP in CA3 pyramidal cells.
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DOI:
10.1038/ncomms13480
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发表时间:
2016-11-16
影响因子:
16.6
通讯作者:
Gerber, Urs
Gerber, Urs
中科院分区:
综合性期刊1区
文献类型:
--
作者:
Brandalise, Federico;Carta, Stefano;Helmchen, Fritjof;Lisman, John;Gerber, Urs

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神经元的计算库通过树突中启动的再生电信号来增强。这些事件,被称为树突棘波,可以作为突触输入的细胞固有放大器。在这些信号中,树突状NMDA尖峰与突触LTP诱导相关。由于不可能在维持NMDA受体启动突触可塑性的同时阻断NMDA锋电位,因此目前尚不清楚单独的NMDA锋电位是否能触发LTP。在这里,我们使用树突状记录和钙成像分析的作用,NMDA棘波在相关的LTP在CA 3锥体细胞。我们发现,NMDA尖峰产生再生分支特定的钙瞬变。降低NMDA尖峰的概率会降低LTP,而增加它们的概率会增强LTP。NMDA尖峰和LTP发生时没有反向传播动作电位。然而,动作电位可以通过促进NMDA峰电位促进LTP的诱导。因此,NMDA尖峰是必要的,足以产生关键的突触后去极化所需的相关LTP在CA 3锥体细胞。 反向传播动作电位(bAP)和NMDA树突棘都与长时程可塑性(LTP)诱导有关,但尚不清楚哪些因素是必不可少的。在这里,利用电生理学和Ca ~(2+)成像,作者发现NMDA锋电位是LTP的关键启动剂,并且bAP的贡献通过NMDA锋电位触发而发生。
The computational repertoire of neurons is enhanced by regenerative electrical signals initiated in dendrites. These events, referred to as dendritic spikes, can act as cell-intrinsic amplifiers of synaptic input. Among these signals, dendritic NMDA spikes are of interest in light of their correlation with synaptic LTP induction. Because it is not possible to block NMDA spikes pharmacologically while maintaining NMDA receptors available to initiate synaptic plasticity, it remains unclear whether NMDA spikes alone can trigger LTP. Here we use dendritic recordings and calcium imaging to analyse the role of NMDA spikes in associative LTP in CA3 pyramidal cells. We show that NMDA spikes produce regenerative branch-specific calcium transients. Decreasing the probability of NMDA spikes reduces LTP, whereas increasing their probability enhances LTP. NMDA spikes and LTP occur without back-propagating action potentials. However, action potentials can facilitate LTP induction by promoting NMDA spikes. Thus, NMDA spikes are necessary and sufficient to produce the critical postsynaptic depolarization required for associative LTP in CA3 pyramidal cells. Back-propagating action potentials (bAP) and NMDA dendritic spikes have both been linked to long-term plasticity (LTP) induction, though it is unclear which factors are essential. Here, using electrophysiology and Ca2+ imaging, the authors find NMDA spikes are a key initiator of LTP, and that bAP contribution occurs via NMDA spike triggering.
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