Modulation of synaptic plasticity by physiological activation of M1 muscarinic acetylcholine receptors in the mouse hippocampus
Modulation of synaptic plasticity by physiological activation of M1 muscarinic acetylcholine receptors in the mouse hippocampus
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DOI：
10.1523/jneurosci.2338-05.2005
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发表时间：
2005-11-30
影响因子：
5.3
通讯作者：
Manabe, T
中科院分区：
文献类型：
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作者：
Shinoe, T;Matsui, M;Manabe, T
毒蕈碱乙酰胆碱受体（mAChR）被认为是调节海马突触可塑性的神经递质受体之一，可能在学习和记忆中起着至关重要的作用。然而，在以往的研究中，毒蕈碱激动剂的使用浓度相对较高，毒蕈碱拮抗剂的亚型选择性并不令人满意。因此，ACh的生理水平是否参与突触可塑性的调节以及哪些mAChR亚型负责这种作用仍有待回答。在本研究中，我们发现低浓度（50 nM）的碳二醇可增强小鼠海马皮层兴奋性突触传递的长期增强（LTP）。值得注意的是，这种增强作用在M-1 mAChR敲除（KO）小鼠中被消除，而在M-3 mAChR KO小鼠中没有，尽管LTP本身在两种突变小鼠中都是完整的。此外，我们发现反复刺激东侧地层（可能会触发胆碱能末端的内源性ACh释放）可以增强野生型小鼠的LTP，而在M-1 mAChR KO小鼠中则没有。这些结果表明，胆碱能纤维生理性释放的乙酰胆碱能通过突触后M-1 mAChR激活调节海马突触可塑性。
The muscarinic acetylcholine receptor (mAChR) has been considered one of the neurotransmitter receptors regulating hippocampal synaptic plasticity, which likely plays a critical role in learning and memory. In previous studies, however, muscarinic agonists were used at relatively high concentrations, and the subtype selectivity of muscarinic antagonists was not satisfactory. Thus, it remains to be answered whether physiological levels of ACh are involved in the regulation of synaptic plasticity and which mAChR subtypes are responsible for such effects. We found in this study that a low concentration (50 nM) of carbachol enhanced long-term potentiation (LTP) of excitatory synaptic transmission in mouse hippocampal slices. Notably, this enhancing effect was abolished in M-1 mAChR knock-out (KO) but not in M-3 mAChR KO mice, although LTP itself was intact in both mutant mice. Furthermore, we found that repetitive stimulation in the stratum oriens, which presumably triggered the release of endogenous ACh from cholinergic terminals, could enhance LTP in wild-type mice but not in M-1 mAChR KO mice. These results suggest that physiologically released ACh from cholinergic fibers modulates hippocampal synaptic plasticity through the postsynaptic M-1 mAChR activation.