Stratum oriens stimulation-evoked modulation of hippocampal long-term potentiation involves the activation of muscarinic acetylcholine receptors and the inhibition of Kv7/M potassium ion channels.
Stratum oriens stimulation-evoked modulation of hippocampal long-term potentiation involves the activation of muscarinic acetylcholine receptors and the inhibition of Kv7/M potassium ion channels.
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定向层刺激诱发的海马长时程增强调节涉及毒蕈碱乙酰胆碱受体的激活和 Kv7/M 钾离子通道的抑制。
DOI：
10.1111/j.1460-9568.2012.08127.x
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发表时间：
2012
影响因子：
3.4
通讯作者：
T.
中科院分区：
文献类型：
--
作者：
Suzuki;E. & Okada;T.
乙酰胆碱被认为是海马神经传递和突触可塑性的内源性调节剂。据报道，毒蕈碱类乙酰胆碱受体（mAChRs）的激活增强了海马突触的可塑性，这在记忆功能中起重要作用；然而，它增强突触可塑性的机制尚不清楚。在这里，我们研究了在mAChR激活诱导的大鼠海马Schaffer侧枝(SC) -CA1突触的长期增强（LTP）过程中，作为mAChR调节靶点的Kv7/M K+通道的抑制参与。在强电刺激SCs之前，对取向层施加电刺激，诱导的SC-CA1突触LTP的大小比未施加取向层刺激的SC-CA1突触LTP的大小增强。在mAChR拮抗剂阿托品存在的情况下，破伤风刺激诱导稳定的LTP，但东面层刺激引起的LTP增强被消除。额外应用XE991，一种Kv7/M K+通道的选择性阻断剂，恢复了阿托品诱导的LTP增强抑制。磷脂酶C （PLC）抑制剂U - 73122抑制了地层刺激引起的LTP增强。T/R型电压依赖性Ca2+通道（VDCC）阻滞剂Ni2+的应用消除了地层取向刺激引起的LTP增强。此外，在n -甲基- d -天冬氨酸受体阻断期间，破伤风刺激和先前的定向层刺激能够诱导LTP。因此，我们提出，地层取向刺激通过mAChR激活诱导PLC激活来抑制Kv7/M K+通道，从而导致VDCC激活，从而导致足够的Ca2+内流来增强LTP。
Acetylcholine is considered to be an endogenous modulator of hippocampal neurotransmission and synaptic plasticity. The activation of muscarinic acetylcholine receptors (mAChRs) reportedly enhances hippocampal synaptic plasticity, which plays an important role in memory function; however, the mechanism by which it enhances synaptic plasticity remains unclear. Here, we examined the involvement of the inhibition of Kv7/M K+channels, which are targets of mAChR modulation, during mAChR activation‐induced enhancement of long‐term potentiation (LTP) at rat hippocampal Schaffer collateral (SC)–CA1 synapses. When an electrical stimulus was applied to the stratum oriens before tetanic stimulation of the SCs, the magnitude of the induced SC–CA1 synapse LTP was enhanced as compared with that induced without stratum oriens stimulation. In the presence of the mAChR antagonist atropine, tetanic stimulation induced stable LTP, but the stratum oriens stimulation‐evoked enhancement of LTP was abolished. The additional application of XE991, a selective blocker of Kv7/M K+channels, rescued the atropine‐induced inhibition of LTP enhancement. The phospholipase C (PLC) inhibitor U‐73122 inhibited the stratum oriens stimulation‐evoked enhancement of LTP. Application of the T/R‐type voltage‐dependent Ca2+channel (VDCC) blocker Ni2+abolished the stratum oriens stimulation‐evoked enhancement of LTP. In addition, tetanic stimulation with preceding stratum oriens stimulation was able to induce LTP duringN‐methyl‐d‐aspartate receptor blockade. We therefore propose that stratum oriens stimulation inhibits Kv7/M K+channels through mAChR activation‐induced PLC activation, which leads to VDCC activation, and hence causes sufficient Ca2+influx to enhance LTP.