Functional connectivity in a novel cerebellar-amygdala circuit that regulates fear extinction

摘要 小脑（CB）长期以来一直被认为是一个纯粹的运动结构;然而，过去几年的研究表明， 几十年来，研究人员也发现了重要的非运动功能，包括在边缘系统处理中的关键作用。的 小脑参与情感体验和控制适当的自主神经， 认知和行为反应，并在情绪记忆的各个阶段发挥重要作用，包括 收购、合并、存储和检索以及消灭。小脑功能障碍 与各种神经和神经精神障碍如认知情感综合征相关， 精神分裂症焦虑症和抑郁症为了在运动和认知领域都取得如此多的成就， 小脑被认为是整合不同的输入，并将有关最佳行为输出的预测发送给大脑。 其余的大脑。然而，参与这类加工的途径和机制仍然很差 明白我的实验室最近发现了连接小脑和小脑的新的双突触通路。 杏仁核通过板内丘脑（Th）（中央内侧核和束旁核）和腹侧被盖 腹侧被盖区（VTA）可能在这些扩展的认知和情感功能中发挥重要作用。的 在这项提议中概述的实验将集中在检查新的小脑-丘脑-杏仁核通路是否 参与了恐惧消退学习，其中关于意外结果的信号被认为是指导变化的信号。 在行为上。在这些实验中，我将使用纤维钙成像来测量通路中的活动 光度学和操纵信号与光遗传学。在切片电生理学实验中，我 将检查CB-Th连接的细胞和突触特性。这项提案将提供 新的见解小脑可能在情绪学习的背景下做什么， 非运动行为中的特定通路，以及每个微电路内的信号传导特性。这些 探索将增加我们对小脑边缘系统功能的理解，并有助于指导未来的研究， 这些回路可能在神经精神障碍中受损，以推动对更有效治疗的探索。

ABSTRACT The cerebellum (CB) has long been considered a purely motor structure; however, studies over the last few decades have revealed vital, non-motor functions as well, including a key role in limbic processing. The cerebellum is involved in both the experience of emotion and in controlling the appropriate autonomic, cognitive, and behavioral responses, and plays an important part in all phases of emotional memory, including acquisition, consolidation, storage and retrieval, and extinction. Dysfunctions of the cerebellum have been associated with various neurological and neuropsychiatric disorders such as cognitive affective syndrome, schizophrenia, anxiety, and depression. To accomplish so much in both the motor and cognitive domains, the cerebellum is thought to integrate diverse inputs and send predictions about optimal behavioral outputs to the rest of the brain. However, the pathways and mechanisms involved in this type of processing remain poorly understood. My lab has recently discovered novel disynaptic pathways connecting the cerebellum and the amygdala via the intralaminar thalamus (Th) (centromedial and parafascicular nuclei) and ventral tegmental area (VTA) which may play a fundamental role in these expanded cognitive and emotional functions. The experiments outlined in this proposal will focus on examining if the novel cerebello-thalamo-amygdala pathway is involved in fear extinction learning, where signals about unexpected outcomes are thought to guide changes in behavior. In these experiments, I will measure activity in the pathway using calcium imaging with fiber photometry and manipulate signaling with optogenetics. In tandem, in slice electrophysiology experiments, I will examine the cellular and synaptic properties of CB-Th connectivity. Together, this proposal will provide novel insights into what the cerebellum might be doing in the context of emotional learning, the necessity of the specific pathway in non-motor behavior, and the signaling properties within each microcircuit. These explorations will add to our understanding of cerebellar limbic functions and help guide future studies of how these circuits may be impaired in neuropsychiatric disorders to propel the search for more effective treatments.