杏仁核—脑桥核投射调控小脑运动学习的机制研究

Interactions between between emotional and motor memory systems play a critical role in complex behavior. Previous studies showed that amygdala activation induced by fear conditioning facilitates cerebellum-dependent eyeblink conditioning, a type of associative motor learning. However, knowledge about when and how the amygdala modulates cerebellar motor learning remains largely unknown. Hence, in this project, we plan to use a combination of advanced techniques, including in vivo optogenetics, in vivo calcium imaging, and in vivo chemogenetics to investigate whether the amygdala is involved in modulating the cerebellar motor learning via its substantial projections to the pontine nuclei under the weak conditioned stimulus. Then, we attempt to test whether the central amygdala–pontine nuclei projections facilitate cerebellar motor learning by increasing the salience of the weak conditioned stimulus signal in the pontine nuclei input to the cerebellum. Clarifying the neural circuit underlying the facilitatory effect of the amygdala on cerebellar motor learning is of great significance for deeper understanding the neural mechanisms underlying learning and memory.

情绪记忆系统和运动记忆系统之间的相互作用对于复杂行为的完成至关重要。研究提示恐惧条件反射导致的杏仁核激活能够促进小脑运动学习（如眨眼条件反射），但是迄今为止对于杏仁核何时以及如何参与小脑运动学习的调控缺乏基本了解。为此，本项目计划联合使用在体光遗传学、在体钙成像、在体化学遗传学等技术，研究杏仁核是否在弱条件刺激下通过到脑桥核的直接投射参与调控小脑运动学习，中央杏仁核到脑桥核的直接投射能否易化条件刺激信号的传递。阐明杏仁核对小脑运动学习的易化作用及其相关通路对于深入理解学习记忆的神经机制具有重要意义。

情绪记忆系统和运动记忆系统之间的相互作用对于复杂行为的完成至关重要。研究提示恐惧条件反射导致的杏仁核激活能够促进小脑运动学习，但是迄今为止对于杏仁核何时以及如何参与小脑运动学习的调控缺乏基本了解。本项目选择延迟性眨眼条件反射为小脑运动学习的行为学模型，采用在体光遗传学、在体钙成像、在体化学遗传学等技术，研究杏仁核是否在弱条件刺激下通过到脑桥核的直接投射参与调控小脑运动学习，中央杏仁核到脑桥核的直接投射能否易化弱条件刺激信号的传递。我们的结果显示：（1）光遗传学和化学遗传学抑制中央杏仁核能明显抑制弱条件刺激引导的延迟性眨眼条件反射，但不影响强条件刺激引导的延迟性眨眼条件反射。（2）光遗传学抑制中央杏仁核到脑桥核的投射能明显抑制弱条件刺激引导的延迟性眨眼条件反射，但不影响强条件刺激引导的延迟性眨眼条件反射，化学遗传学抑制中央杏仁核到脑桥核的投射神经元也能干扰弱条件刺激引导的延迟性眨眼条件反射。（3）化学遗传学抑制中央杏仁核能降低脑桥核神经元对弱条件刺激信号的钙活动反应。综上所述，本项目阐明了杏仁核何时以及如何参与易化小脑运动学习，这对于我们深入理解学习记忆的神经机制具有重要意义。