Neural Pathways for Conditioned Stimuli in Eyeblink Conditioning

描述（由申请人提供）：小脑及其与大脑其他部分的连接作为功能回路，是运动控制、学习、注意力、语言、工作记忆和情感等各个方面的基础。这些功能回路的破坏可能是精神分裂症、双相情感障碍、自闭症、脆性X染色体综合征和其他疾病症状的基础。目前的建议旨在检查学习所必需的小脑的感觉输入，并确定小脑是否在学习过程中向这些感觉输入发送反馈。巴甫洛夫眨眼条件反射将被用作评估小脑学习的方法。该项目先前的研究结果确定了听觉眨眼条件反射所必需的神经通路，其中包括内侧听觉丘脑（MAT）及其向脑桥核的投射。MAT神经元在眨眼过程中表现出与学习相关的活动变化，这种变化被假设是由小脑的反馈驱动的。目前的第一个目标是确定视觉眨眼条件反射所必需的神经通路，并确定视觉丘脑是否也显示学习相关的活动，使用可逆失活和高密度神经元记录方法。目的2是通过记录丘脑的神经元活动，同时使小脑及其靶核失活，来确定丘脑中与学习相关的活动是否由小脑或其下游靶核驱动。目的3将利用高密度神经元记录方法研究小脑学习的跨模态促进机制。目的4是通过可逆失活来确定大脑皮层听觉和视觉区域在小脑学习中的作用。拟议的项目将大大增加

DESCRIPTION (provided by applicant): The cerebellum and its connections with other parts of the brain act as functional loops that underlie various aspects of motor control, learning, attention, language, working memory, and emotion. Disruption of these functional loops may be the basis for symptoms of schizophrenia, bipolar disorder, autism, fragile X syndrome, and other disorders. The current proposal is designed to examine sensory inputs to the cerebellum that are necessary for learning and to determine whether the cerebellum sends feedback to these sensory inputs during learning. Pavlovian eyeblink conditioning will be used as the method for assessing cerebellar learning. Previous findings from this project identified the neural pathway necessary for auditory eyeblink conditioning, which includes the medial auditory thalamus (MAT) and its projections to the pontine nuclei. MAT neurons exhibit learning-related changes in activity during eyeblink conditioning that are hypothesized to be driven by feedback from the cerebellum. The first aim of the current proposal is to identify the neural pathway(s) necessary for visual eyeblink conditioning and to determine whether the visual thalamus also shows learning-related activity using reversible inactivation and high-density neuronal recording methods. Aim 2 is to determine whether learning-related activity in the thalamus is driven by the cerebellum or its downstream target nuclei by recording neuronal activity in the thalamus while inactivating the cerebellum and its target nuclei. Aim 3 will investigate the mechanisms underlying cross-modal facilitation of cerebellar learning using high- density neuronal recording methods. Aim 4 is to determine the roles of auditory and visual areas of the cerebral cortex in cerebellar learning using reversible inactivation. The proposed project will significantly increase knowledge about the nature of cerebellar interactions with sensory areas of the brain that underlie associative learning. Findings from this project could be used to develop methods for treating various symptoms caused by pathology in cerebellar interactions with other brain areas. PUBLIC HEALTH RELEVANCE: The cerebellum and its connections with other brain areas act as functional loops that contribute to movement, attention, working memory, learning, timing perception, language, and executive control. Pathology in the cerebellum or its connections with other brain areas may be the basis for the symptoms of schizophrenia, bipolar disorder, fragile X syndrome, autism, and other disorders. The proposed research will examine the mechanisms of cerebellar interactions with sensory systems. The findings of this project could be used to develop methods for treating various symptoms caused by pathology in cerebellar interactions with other brain areas.