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A novel output pathway from the cerebellum for regulation of diverse non-motor behaviors

小脑调节多种非运动行为的新型输出途径

基本信息

批准号：
10327320
负责人：
WADE G REGEHR
金额：
$ 56.56万
依托单位：
HARVARD MEDICAL SCHOOL
依托单位国家：
美国
项目类别：
财政年份：
2020
资助国家：
美国
起止时间：
2020-03-01 至 2024-12-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/10327320
关键词：
Address Aggressive behavior Amygdaloid structure Anatomy Animal Model Behavior Brain region Breathing Caliber Cerebellar Cortex Cerebellar Nuclei Cerebellar vermis structure Cerebellum Cholera Toxin Protomer B Desire for food Epilepsy Extinction (Psychology)Fright Heart Rate Hippocampus (Brain)Human Hypothalamic structure Image Impairment In Situ Hybridization Label Lead Medial Mediating Motor Motor Pathways Mus Neurons Output Pathway interactions Post-Traumatic Stress Disorders Prevalence Pupil Purkinje Cells Regulation Rewards Role Short-Term Memory Signal Transduction Slice Social Behavior Synapses Testing Thalamic structure awake basal forebrain base behavior influence cell type conditioned fear high resolution imaging in vivo insight motor learning nervous system disorder novel optogenetics parabrachial nucleus targeted imaging

项目摘要

Abstract/Summary In addition to its well-established role in motor function and motor learning, the cerebellum is implicated in a myriad of non-motor behaviors. In humans, cerebellar damage can impair abstract reasoning and working memory, and result in PTSD. In animal models, the cerebellum regulates heart rate, breathing, aggression, appetite, fear conditioning and many other behaviors. In general, the role of the cerebellum in regulating these behaviors is not well understood. An important step in understanding these nonmotor behaviors is to determine the output pathway and downstream targets that allow the cerebellum to regulate these behaviors. It is known that Purkinje cells (PCs) relay signals from the cerebellar cortex to the deep cerebellar nuclei (DCN), which in turn activate the motor thalamus. It was assumed that DCN outputs are also responsible for nonmotor behaviors. Here, we describe powerful and direct inhibitory connections between PCs in regions of the cerebellum implicated in nonmotor behaviors, and neurons in the parabrachial nucleus (PBN). This is intriguing, because the PBN contributes to many of the same nonmotor behaviors influenced by the cerebellum. Based on our preliminary findings, we hypothesize that the PBN is a specialized cerebellar output that allows the cerebellum to regulate nonmotor behaviors. The first step in testing this hypothesis will be to characterize the connections between PCs and the PBN. The studies will determine the strength and prevalence of the direct PC to PBN synapse and determine the extent to which PCs regulate the activity of neurons in the PBN. The second major step is to identify the regions targeted by the PCPBN pathway and to determine the contribution of this pathway to various behaviors. Preliminary studies suggest that this pathway projects to the hypothalamus, the amygdala, and the basal forebrain, and thus has the appropriate connectivity to allow the cerebellum to regulate diverse behaviors ranging from aggression to fear extinction. This promises to lead to a new appreciation of the roles of the cerebellum in numerous behaviors, it will provide insight into the circuits involved in these behaviors and it has important implications for many neurological disorders.

抽象/总结