Enhanced aversive memory retrieval by chemogenetic activation of locus coeruleus norepinephrine neurons

Abstract: The ability to retrieve memory store in response to the environment is essential for animal behavioral adaptation. Norepinephrine (NE)-containing neurons in the brain play a key role in the modulation of synaptic plasticity underlying various processes of memory formation. However, the role of the central NE system in memory retrieval remains unclear. In this study, we developed a neural chemogenetic activation strategy using insect olfactory Ionotropic Receptors (IRs), and used it for selective stimulation of NE neurons in the locus coeruleus (LC) in transgenic mice. Ligand-induced activation of LC NE neurons resulted in enhancement of the retrieval process of conditioned taste aversion, which was mediated through at least partly adrenergic receptors in the amygdala. Pharmacological blockade of LC activity confirmed the facilitative role of these neurons in memory retrieval. Our findings indicate that the LC-amygdalar pathway is required and sufficient for enhancing the recall of taste associative memory.

摘要：动物行为适应依赖于对环境响应时从记忆库中提取信息的能力。脑内含有去甲肾上腺素（NE）的神经元在调节与记忆形成相关的一系列过程的突触可塑性中发挥着关键作用。然而，中枢NE系统在记忆提取过程中的作用尚不明确。在本研究中，我们开发了一种利用昆虫嗅觉离子型受体（IR）的神经化学遗传激活策略，并将其应用于转基因小鼠中缝核（LC）NE神经元的特异性刺激。配体诱导的LC NE神经元激活导致条件味觉厌恶的提取过程增强，这一过程至少部分是通过杏仁核中的肾上腺素能受体介导的。对LC活动的药理学阻断证实了这些神经元在记忆提取过程中的促进作用。我们的研究结果表明，LC-杏仁核通路对于增强味觉联想记忆的回忆是必要且充分的。