HCN1 channels reduce the rate of exocytosis from a subset of cortical synaptic terminals.
HCN1 channels reduce the rate of exocytosis from a subset of cortical synaptic terminals.
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HCN1 通道降低皮质突触末梢子集的胞吐率
DOI：
10.1038/srep40257
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发表时间：
2017-01-10
影响因子：
4.6
通讯作者：
Shah MM
中科院分区：
文献类型：
--
作者：
Huang Z;Li G;Aguado C;Lujan R;Shah MM
超极化激活的环核苷酸门控（HCN 1）通道主要位于皮质内的锥体细胞树突中。最近的证据表明，这些通道也存在于突触前的一个子集内的成熟内嗅皮层（EC）的突触终端。突触前HCN通道的抑制增强EC层III锥体神经元上的微型兴奋性突触后电流（mEPSC），表明这些通道减少神经递质谷氨酸的释放。因此，突触前HCN通道是否改变突触囊泡胞吐的速率，从而增强神经递质的释放？为了解决这个问题，我们成像释放FM 1 -43，一种染料，被纳入突触囊泡，从EC突触末梢使用双光子显微镜切片从前脑特异性HCN 1缺陷小鼠，全球HCN 1基因敲除及其野生型同窝出生。这与电生理学和药理学相结合表明，HCN 1通道限制了EC内皮质突触末端子集的胞吐速率，并以这种方式限制了非动作电位依赖性和动作电位依赖性自发释放以及同步诱发释放。由于HCN 1通道也影响突触后电位动力学和整合，我们的研究结果表明，有不同的方式，HCN 1通道影响突触的强度和可塑性。
The hyperpolarization-activated cyclic nucleotide-gated (HCN1) channels are predominantly located in pyramidal cell dendrites within the cortex. Recent evidence suggests these channels also exist pre-synaptically in a subset of synaptic terminals within the mature entorhinal cortex (EC). Inhibition of pre-synaptic HCN channels enhances miniature excitatory post-synaptic currents (mEPSCs) onto EC layer III pyramidal neurons, suggesting that these channels decrease the release of the neurotransmitter, glutamate. Thus, do pre-synaptic HCN channels alter the rate of synaptic vesicle exocytosis and thereby enhance neurotransmitter release? To address this, we imaged the release of FM1-43, a dye that is incorporated into synaptic vesicles, from EC synaptic terminals using two photon microscopy in slices obtained from forebrain specific HCN1 deficient mice, global HCN1 knockouts and their wildtype littermates. This coupled with electrophysiology and pharmacology showed that HCN1 channels restrict the rate of exocytosis from a subset of cortical synaptic terminals within the EC and in this way, constrain non-action potential-dependent and action potential-dependent spontaneous release as well as synchronous, evoked release. Since HCN1 channels also affect post-synaptic potential kinetics and integration, our results indicate that there are diverse ways by which HCN1 channels influence synaptic strength and plasticity.