A cholinergic trigger drives learning-induced plasticity at hippocampal synapses.
A cholinergic trigger drives learning-induced plasticity at hippocampal synapses.
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DOI：
10.1038/ncomms3760
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发表时间：
2013
影响因子：
16.6
通讯作者：
Takahashi, Takuya
中科院分区：
文献类型：
--
作者：
Mitsushima, Dai;Sano, Akane;Takahashi, Takuya
学习诱发突触的可塑性变化。然而，协调学习诱导的突触变化的调节分子在很大程度上是未知的。虽然内侧隔的胆碱能输入调节学习和记忆已被公认，但缺乏胆碱能调节学习诱导的突触可塑性的证据。在这里，我们发现，毒蕈碱乙酰胆碱（ACh）受体（mAChRs）的激活介导的上下文恐惧学习驱动的加强海马兴奋性锥体突触通过突触纳入AMPA型谷氨酸受体（AMPAR）。情境性恐惧学习也增强了海马锥体CA1神经元上抑制性突触的强度，其方式是由烟碱型乙酰胆碱受体（nAChRs）而不是mAChRs的激活介导的。我们观察到学习诱导的兴奋性和抑制性突触强度在个别锥体神经元的增加之间的显着相关性。了解胆碱能调节学习诱导的海马突触可塑性的机制可能有助于开发认知障碍的新疗法。 胆碱能信号调节学习和记忆，然而，它对学习诱导的突触可塑性的影响不太清楚。Mitsushima等人表明，在抑制性回避任务后，乙酰胆碱同时加强了CA1锥体神经元上的兴奋性和抑制性突触。
Learning induces plastic changes in synapses. However, the regulatory molecules that orchestrate learning-induced synaptic changes are largely unknown. Although it is well established that cholinergic inputs from the medial septum modulate learning and memory, evidence for the cholinergic regulation of learning-induced synaptic plasticity is lacking. Here we find that the activation of muscarinic acetylcholine (ACh) receptors (mAChRs) mediates the contextual fear learning-driven strengthening of hippocampal excitatory pyramidal synapses through the synaptic incorporation of AMPA-type glutamate receptors (AMPARs). Contextual fear learning also enhances the strength of inhibitory synapses on hippocampal pyramidal CA1 neurons, in a manner mediated by the activation of, not mAChRs, but, nicotinic AChRs (nAChRs). We observe a significant correlation between the learning-induced increases in excitatory and inhibitory synaptic strength at individual pyramidal neurons. Understanding the mechanisms underlying cholinergic regulation of learning-induced hippocampal synaptic plasticity may help the development of new therapies for cognitive disorders. Cholinergic signalling modulates learning and memory; however, its influence on learning-induced synaptic plasticity is less clear. Mitsushima et al. show that acetylcholine simultaneously strengthens both excitatory and inhibitory synapses onto CA1 pyramidal neurons following an inhibitory avoidance task.
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