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.

海马体中乙酰胆碱的释放在新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 CA1 中对来自内嗅皮层的新感觉信息的反应，同时抑制来自 CA3 中先前编码表示的输入。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，来自内嗅皮层的前馈抑制表现出比 CA3 更大的抑制作用，导致内嗅输入选择性增强兴奋-抑制平衡和 CA1 激活。₃和 M ₄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考虑向 CA1 输入新信息的作用和机制。