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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乙酰胆碱通过前馈抑制电路的差分调制优先考虑从内嗅皮层到 CA1 的直接突触输入

DOI:
10.1101/2020.01.20.912873
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发表时间:
2020
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影响因子:
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通讯作者:
Palacios-Filardo J
Palacios-Filardo J
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作者:
Palacios-Filardo J

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海马区的乙酰胆碱释放在形成新的记忆表征中起着核心作用。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CA1对来自内嗅皮层的新感觉信息的反应,同时抑制CA3中先前编码的表征的输入。在这里,我们表明,来自内嗅皮层和CA3的兴奋性输入同样受到CA1中乙酰胆碱突触释放的抑制。然而,来自内嗅觉皮质的前馈抑制比CA3表现出更大的抑制,从而选择性地增强兴奋-抑制平衡和内嗅觉输入对CA1的激活。内嗅神经通路和CA3通路涉及不同的前馈中间神经元亚群,胆碱能对突触前功能的调节分别由M受体M3和M4不同地介导。因此,我们的数据支持乙酰胆碱在记忆形成过程中优先考虑新信息输入到CA1的作用和机制。
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 M3and M4receptors, respectively. Thus, our data support a role and mechanisms for acetylcholine to prioritise novel information inputs to CA1 during memory formation.
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