Neural Pathways for Conditioned Stimuli in Eyeblink Conditioning

描述(申请人提供)：小脑及其与大脑其他部分的连接是构成运动控制、学习、注意力、语言、工作记忆和情绪的各个方面的功能环路。这些功能环的中断可能是精神分裂症、双相情感障碍、自闭症、脆性X综合征和其他疾病症状的基础。目前的建议旨在检查小脑的感觉输入是学习所必需的，并确定小脑在学习过程中是否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。该项目以前的发现确定了听觉眨眼条件反射所需的神经通路，其中包括内侧听觉丘脑(MAT)及其向桥核的投射。MAT神经元在眨眼条件反射过程中表现出与学习相关的活动变化，这种变化被认为是由小脑的反馈驱动的。本方案的第一个目的是确定视觉眨眼条件反射所必需的神经通路(S)，并利用可逆失活和高密度神经元记录方法确定视觉丘脑是否也显示出与学习相关的活动。目的2是通过记录丘脑中神经元的活动来确定丘脑中与学习相关的活动是否由小脑或其下游的靶核驱动，同时使小脑及其靶核失活。目的3将使用高密度神经元记录方法研究小脑学习跨模式易化的潜在机制。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。拟议中的项目将大幅增加 了解小脑与大脑感觉区域相互作用的性质，这是联想学习的基础。这个项目的发现可以用来开发治疗小脑与其他大脑区域相互作用的病理引起的各种症状的方法。 与公共健康相关：小脑及其与其他大脑区域的连接充当功能环路，有助于运动、注意力、工作记忆、学习、时间感知、语言和执行控制。小脑的病理或其与其他大脑区域的联系可能是精神分裂症、双相情感障碍、脆性X综合征、自闭症和其他疾病症状的基础。这项拟议的研究将研究小脑与感觉系统相互作用的机制。这个项目的发现可以用来开发治疗小脑与其他大脑区域相互作用的病理引起的各种症状的方法。

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.