Acetylcholine prioritises direct synaptic inputs from entorhinal cortex to CA1 by differential modulation of feedforward inhibitory circuits.
Acetylcholine prioritises direct synaptic inputs from entorhinal cortex to CA1 by differential modulation of feedforward inhibitory circuits.
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DOI：
10.1038/s41467-021-25280-5
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发表时间：
2021-09-16
影响因子：
16.6
通讯作者：
Mellor JR
中科院分区：
文献类型：
--
作者：
Palacios-Filardo J;Udakis M;Brown GA;Tehan BG;Congreve MS;Nathan PJ;Brown AJH;Mellor JR
海马体中乙酰胆碱的释放在新的记忆表征的形成中起着核心作用。一个有影响力但基本上未经检验的理论提出，记忆的形成需要乙酰胆碱来增强CA 1对来自内嗅皮层的新感觉信息的反应，同时抑制来自CA 3中先前编码的表征的输入。在这里，我们表明，兴奋性输入内嗅皮层和CA 3同样受到抑制的突触释放的乙酰胆碱在CA 1。然而，从内嗅皮层前馈抑制表现出更大的抑郁症比CA 3兴奋-抑制平衡和CA 1激活内嗅输入的选择性增强。内嗅和CA 3途径参与不同的前馈中间神经元亚群和胆碱能调节突触前功能的差异介导的毒蕈碱M3和M4受体，分别。因此，我们的数据支持乙酰胆碱在记忆形成过程中优先向CA 1输入新信息的作用和机制。在这项研究中，乙酰胆碱释放重组海马CA 1区抑制网络，导致内嗅输入优先于CA 3输入。这是通过激活M3和M4毒蕈碱受体的组合来实现的。
Acetylcholine release in the hippocampus plays a central role in the formation of new memory representations. An influential but largely untested theory proposes that memory formation requires acetylcholine to enhance responses in CA1 to new sensory information from entorhinal cortex whilst depressing inputs from previously encoded representations in CA3. Here, we show that excitatory inputs from entorhinal cortex and CA3 are depressed equally by synaptic release of acetylcholine in CA1. However, feedforward inhibition from entorhinal cortex exhibits greater depression than CA3 resulting in a selective enhancement of excitatory-inhibitory balance and CA1 activation by entorhinal inputs. Entorhinal and CA3 pathways engage different feedforward interneuron subpopulations and cholinergic modulation of presynaptic function is mediated differentially by muscarinic M3 and M4 receptors, respectively. Thus, our data support a role and mechanisms for acetylcholine to prioritise novel information inputs to CA1 during memory formation. In this study, acetylcholine release is shown to reorganise hippocampal CA1 inhibitory networks resulting in prioritisation of entorhinal input over CA3 input. This is achieved by activation of a combination of M3 and M4 muscarinic receptors.
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影响因子：
16.2
作者：
Gu Z;Yakel JL
通讯作者：
Yakel JL
DOI：
10.1093/cercor/bhv227
发表时间：
2016-01
期刊：
Cerebral cortex (New York, N.Y. : 1991)
影响因子：
--
作者：
Dennis SH;Pasqui F;Colvin EM;Sanger H;Mogg AJ;Felder CC;Broad LM;Fitzjohn SM;Isaac JT;Mellor JR
通讯作者：
Mellor JR
DOI：
10.1111/ejn.13582
发表时间：
2017-06
期刊：
The European journal of neuroscience
影响因子：
--
作者：
Betterton RT;Broad LM;Tsaneva-Atanasova K;Mellor JR
通讯作者：
Mellor JR
影响因子：
3.5
作者：
Dannenberg H;Young K;Hasselmo M
通讯作者：
Hasselmo M
影响因子：
5.3
作者：
Ceolin, Laura;Kantamneni, Sriharsha;Lodge, David
通讯作者：
Lodge, David