Bratsch-Prince Joshua X, Jones Grace C, Warren James W, Mott David D
Department of Pharmacology, Physiology & Neuroscience, University of South Carolina School of Medicine, Columbia, South Carolina, 29208, USA.
bioRxiv. 2024 Dec 2:2024.12.01.626291. doi: 10.1101/2024.12.01.626291.
While the basolateral amygdala (BLA) is critical in the consolidation of emotional memories, mechanisms underlying memory consolidation in this region are not well understood. In the hippocampus, memory consolidation depends upon network signatures termed sharp wave ripples (SWR). These SWRs largely occur during states of awake rest or slow wave sleep and are inversely correlated with cholinergic tone. While high frequency cholinergic stimulation can inhibit SWRs through muscarinic acetylcholine receptors, it is unclear how nicotinic acetylcholine receptors or different cholinergic firing patterns may influence SWR generation. SWRs are also present in BLA . Interestingly, the BLA receives extremely dense cholinergic inputs, yet the relationship between acetylcholine (ACh) and BLA SWRs is unexplored. Here, using brain slice electrophysiology in male and female mice, we show that brief stimulation of ACh inputs to BLA reliably induces SWRs that resemble those that occur in the BLA . Repeated ACh-SWRs are induced with single pulse stimulation at low, but not higher frequencies. ACh-SWRs are driven by nicotinic receptors which recruit different classes of local interneurons and trigger glutamate release from external inputs. In total, our findings establish a previously undefined mechanism for SWR induction in the brain. They also challenge the previous notion of neuromodulators as purely modulatory agents gating these events but instead reveal these systems can directly instruct SWR induction with temporal precision. Further, these results intriguingly suggest a new role for the nicotinic system in emotional memory consolidation.
虽然基底外侧杏仁核(BLA)在情绪记忆巩固中起关键作用,但该区域记忆巩固的潜在机制尚未完全明确。在海马体中,记忆巩固依赖于被称为尖波涟漪(SWR)的网络信号。这些SWR主要出现在清醒休息或慢波睡眠状态期间,并且与胆碱能张力呈负相关。虽然高频胆碱能刺激可通过毒蕈碱型乙酰胆碱受体抑制SWR,但尚不清楚烟碱型乙酰胆碱受体或不同的胆碱能放电模式如何影响SWR的产生。SWR在BLA中也存在。有趣的是,BLA接受极其密集的胆碱能输入,但乙酰胆碱(ACh)与BLA的SWR之间的关系尚未得到探索。在这里,我们利用雄性和雌性小鼠的脑片电生理学方法,表明对BLA的ACh输入进行短暂刺激可可靠地诱导出与BLA中出现的类似的SWR。在低频而非高频下,单脉冲刺激可诱导重复的ACh-SWR。ACh-SWR由烟碱型受体驱动,这些受体募集不同类型的局部中间神经元并触发来自外部输入的谷氨酸释放。总的来说,我们的研究结果确立了一种先前未定义的大脑中SWR诱导机制。它们还挑战了之前将神经调质视为仅对这些事件起门控作用的调节因子的观点,而是揭示这些系统可以以时间精度直接指导SWR的诱导。此外,这些结果有趣地暗示了烟碱系统在情绪记忆巩固中的新作用。