Center for Synaptic Plasticity, School of Physiology, Pharmacology and Neuroscience, University of Bristol, University Walk, Bristol, UK.
Sosei Heptares, Steinmetz Building, Granta Park, Great Abingdon, Cambridge, UK.
Nat Commun. 2021 Sep 16;12(1):5475. doi: 10.1038/s41467-021-25280-5.
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 M and M receptors, respectively. Thus, our data support a role and mechanisms for acetylcholine to prioritise novel information inputs to CA1 during memory formation.
海马体中的乙酰胆碱释放在新记忆表象的形成中起着核心作用。一个有影响力但在很大程度上未经检验的理论提出，记忆形成需要乙酰胆碱增强 CA1 对来自内嗅皮层的新感觉信息的反应，同时抑制来自 CA3 中先前编码表象的输入。在这里，我们表明，来自内嗅皮层和 CA3 的兴奋性输入在 CA1 中的乙酰胆碱突触释放的作用下被同等抑制。然而，来自内嗅皮层的前馈抑制比 CA3 表现出更大的抑制作用，导致兴奋性-抑制性平衡和 CA1 对来自内嗅皮层输入的激活选择性增强。内嗅皮层和 CA3 通路涉及不同的前馈中间神经元亚群，而胆碱能对突触前功能的调制分别由毒蕈碱 M 和 M 受体介导。因此，我们的数据支持乙酰胆碱在记忆形成过程中优先处理 CA1 中新颖信息输入的作用和机制。
