Hippocampal knockdown of α2 nicotinic or M1 muscarinic acetylcholine receptors in C57BL/6J male mice impairs cued fear conditioning.,Genes, Brain and Behavior

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Hippocampal knockdown of α2 nicotinic or M1 muscarinic acetylcholine receptors in C57BL/6J male mice impairs cued fear conditioning.
Genes, Brain and Behavior ( IF 2.4 ) Pub Date : 2020-05-24 , DOI: 10.1111/gbb.12677
Yann S Mineur ₁ , Charlotte Ernstsen ₁ , Ashraful Islam ₁ , Kathrine Lefoli Maibom ₁ , Marina R Picciotto ₁

Affiliation

Acetylcholine (ACh) signaling in the hippocampus is important for behaviors related to learning, memory and stress. In this study, we investigated the role of two ACh receptor subtypes previously shown to be involved in fear and anxiety, the M1 mAChR and the α2 nAChR, in mediating the effects of hippocampal ACh on stress‐related behaviors. Adeno‐associated viral vectors containing short‐hairpin RNAs targeting M1 or α2 were infused into the hippocampus of male C57BL/6J mice, and behavior in a number of paradigms related to stress responses and fear learning was evaluated. There were no robust effects of hippocampal M1 mAChR or α2 nAChR knockdown (KD) in the light/dark box, tail suspension, forced swim or novelty‐suppressed feeding tests. However, effects on fear learning were observed in both KD groups. Short term learning was intact immediately after training in all groups of mice, but both the M1 and α2 hippocampal knock down resulted in impaired cued fear conditioning 24 h after training. In addition, there was a trend for a deficit in contextual memory the M1 mAChR KD group 24 h after training. These results suggest that α2 nicotinic and M1 muscarinic ACh receptors in the hippocampus contribute to fear learning and could be relevant targets to modify brain circuits involved in stress‐induced reactivity to associated cues.

中文翻译：

在C57BL / 6J雄性小鼠中，海马敲除α2烟碱或M1毒蕈碱型乙酰胆碱受体会削弱提示的恐惧条件。

海马中的乙酰胆碱（ACh）信号对于与学习，记忆和压力有关的行为很重要。在这项研究中，我们调查了先前显示出与恐惧和焦虑有关的两种ACh受体亚型M1 mAChR和α2nAChR在介导海马ACh对应激相关行为的影响中的作用。将含有靶向M1或α2的短发夹RNA的腺相关病毒载体注入雄性C57BL / 6J小鼠的海马体中，并评估了与应激反应和恐惧学习有关的许多范例中的行为。在明/暗盒，尾部悬架，强迫游泳或新奇抑制的喂养试验中，海马M1 mAChR或α2nAChR敲低（KD）均无明显作用。然而，在两个KD组中均观察到对恐惧学习的影响。训练所有组的小鼠后，短期学习立即保持完整，但是训练后24小时，M1和α2海马敲除均导致暗示的恐惧条件受损。此外，训练后24小时，M1 mAChR KD组的上下文记忆有减少的趋势。这些结果表明，海马中的α2烟碱型和M1毒蕈碱型ACh受体有助于恐惧学习，并且可能是修饰与应激诱导的对相关线索反应性相关的大脑回路的相关靶标。

更新日期：2020-07-23

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