PDF(Pubmed)
Abstract：
Acetylcholine (ACh) is released from basal forebrain cholinergic neurons in response to salient stimuli and engages brain states supporting attention and memory. These high ACh states are associated with theta oscillations, which synchronize neuronal ensembles. Theta oscillations in the basolateral amygdala (BLA) in both humans and rodents have been shown to underlie emotional memory, yet their mechanism remains unclear. Here, using brain slice electrophysiology in male and female mice, we show large ACh stimuli evoke prolonged theta oscillations in BLA local field potentials that depend upon M3 muscarinic receptor activation of cholecystokinin (CCK) interneurons (INs) without the need for external glutamate signaling. Somatostatin (SOM) INs inhibit CCK INs and are themselves inhibited by ACh, providing a functional SOM→CCK IN circuit connection gating BLA theta. Parvalbumin (PV) INs, which can drive BLA oscillations in baseline states, are not involved in the generation of ACh-induced theta, highlighting that ACh induces a cellular switch in the control of BLA oscillatory activity and establishes an internally BLA-driven theta oscillation through CCK INs. Theta activity is more readily evoked in BLA over the cortex or hippocampus, suggesting preferential activation of the BLA during high ACh states. These data reveal a SOM→CCK IN circuit in the BLA that gates internal theta oscillations and suggest a mechanism by which salient stimuli acting through ACh switch the BLA into a network state enabling emotional memory.
摘要：
乙酰胆碱（ACh）响应于显着刺激而从基底前脑胆碱能神经元释放，并参与支持注意力和记忆的大脑状态。这些高ACh状态与θ振荡有关，同步神经元集合。人类和啮齿动物的基底外侧杏仁核（BLA）中的Theta振荡已被证明是情感记忆的基础，但其机制尚不清楚。这里,在雄性和雌性小鼠中使用脑切片电生理学，我们显示，大的ACh刺激会引起BLA局部场电位的延长theta振荡，这取决于胆囊收缩素（CCK）中间神经元（INs）的M3毒蕈碱受体激活，而无需外部谷氨酸信号传导。生长抑素（SOM）INs抑制CCKINs，本身被ACh抑制，提供功能SOM-CCK在电路连接选通BLAθ。小白蛋白(PV)INs，可以在基线状态下驱动BLA振荡，不参与ACh诱导θ的产生，强调ACh在控制BLA振荡活动中诱导细胞开关，并通过CCKIN建立内部BLA驱动的theta振荡。Theta活动更容易在皮质或海马的BLA中引起，提示在高ACh状态下BLA优先激活。这些数据揭示了BLA中的SOM-CCKIN电路，该电路可控制内部theta振荡，并提出了一种机制，通过ACh作用的显着刺激将BLA转换为网络状态，从而实现情绪记忆。重要性陈述虽然ACh在建立能够实现情绪行为的网络状态方面发挥着关键作用，ACh对涉及情绪过程的电路的作用机制尚不清楚.BLA接受密集的胆碱能投射，并在情绪行为中起关键作用。使用小鼠脑切片中的电生理记录，我们表明胆碱能刺激容易通过CCK诱导BLA中的theta振荡，但不是PVIN。这些振荡由SOMINs门控，在theta振荡的产生中建立CCK-SOM微电路。Further,与海马或皮质相比，BLA中的振荡活动更容易诱导。这些结果揭示了BLAtheta振荡ACh调制的详细电路特定机制，该机制在情绪处理中起着关键作用。
