Role of the cerebellum in temporal processing

小脑在时间处理中的作用

• 批准号: 9018605
• 负责人: ERIC J LANG
• 金额: $ 25.43万
• 依托单位: NEW YORK UNIVERSITY SCHOOL OF MEDICINE
• 依托单位国家: 美国
• 财政年份: 2015
• 资助国家: 美国
• 起止时间: 2015-09-15 至 2017-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9018605
• 关键词: Address; Affect; Affective; Animals; Autistic Disorder; Automobile Driving; Behavior; Behavioral; Brain; Brain Injuries; Brain region; Cell Nucleus; Cells; Cerebellar cortex structure; Cerebellum; Cerebrum; Characteristics; Code; Cognition Disorders; Cognitive; Cognitive deficits; Data; Decision Making; Dentate nucleus; Devices; Discrimination; Disease; Dura Mater; Fetal Alcohol Syndrome; Functional disorder; Goals; Human; Investigation; Judgment; Lateral; Learning; Left; Lesion; Measures; Mental disorders; Movement; Muscle Contraction; Nature; Neurons; Nuclear; Output; Pathway interactions; Pattern; Perception; Physiologic pulse; Pitch Discrimination; Prefrontal Cortex; Probability; Process; Psychometrics; Rattus; Research; Rodent; Role; Sampling; Schizophrenia; Series; Shapes; Short-Term Memory; Signal Transduction; Stimulus; System; Task Performances; Techniques; Testing; Time; Time Perception; Training; Work; awake; base; behavioral study; cerebellar lesion; cognitive function; cognitive task; extracellular; falls; improved; information processing; light intensity; memory process; motor control; motor deficit; nervous system disorder; neurophysiology; optogenetics; public health relevance; research study; response; theories

 DESCRIPTION (provided by applicant): The traditional view of the cerebellum as being essential only for the control of movement is being increasingly challenged by findings that implicate it in cognitive and affective functions, and as a result, motor deficits that occur with cerebellar lesions are now being thought of in more generalized and extended forms as the basis of various cognitive and psychiatric disorders. Recent work indicates cognitive functions, and in particular, time perception, likely depend on interactions between the cerebellum and the prefrontal cortex; however, these interactions, and their derangement in disease states, are not understood. Recent anatomical studies have shown the lateral cerebellum, in particular, is strongly interconnected with other brain regions involved in processing temporal information (e.g., prefrontal cortex), and these pathways provide a substrate for the cerebellum's participation in a network involved in temporal information processing; however, little is known about the information conveyed from the cerebellum to other parts of this network. Thus, the goal of the proposed experiments is to investigate the function of the cerebellar-prefrontal cortical circuits in timing behavior to provide a basis for understanding how cerebellar damage leads to cognitive deficits. The cerebellum is thought to be critical for temporal processing, particularly for short durations (<1 second); however, decisions based on this temporal information require prefrontal cortex involvement. Thus, there must be a dedicated system involving the transfer of this information from cerebellum to the prefrontal cortex. We will investigate how the cerebellum encodes temporal information about a stimulus and how it transfers this information to the prefrontal cortex for storage in working memory and ultimately for making decisions. In addition, we will investigate whether continued cerebellar input is necessary for the proper functioning of the prefrontal circuits involved in working memory and decision-making. To address these issues we will use rodents trained to discriminate stimuli based on temporal (duration) and nontemporal (e.g., pitch of a tone) characteristics. In the first aim, optogenetic techniques will be used to manipulate in a precisely timed manner the actual signals (i.e., the activity of the dentate nucleus cells) that leave the cerebellum in order to investigate the effects on the timing judgments of the animal. The resulting alterations in behavior should provide information about how the cerebellum computes temporal information, when it transfers that information to the prefrontal cortex, and whether cerebellar activity affect memory processes in the prefrontal cortex. In the second aim we will obtain extracellular recordings of the activity of the dentate nuclear neurons during performance of the task to investigate the specific encoding of temporal information by the cerebellum. Such information would significantly improve our understanding of how the cerebellum and cerebrum interact, and of how dysfunction of the cerebellum and prefrontal cortex leads to a variety of neurological and psychiatric disorders and diseases.

 描述（由申请人提供）：小脑仅对运动控制至关重要的传统观点正日益受到暗示小脑在认知和情感功能中的发现的挑战，因此，小脑病变引起的运动缺陷现在被认为以更普遍和更广泛的形式作为各种认知和精神疾病的基础，最近的研究表明认知功能，特别是时间感知，可能取决于小脑和前额叶之间的相互作用。然而，最近的解剖学研究表明，小脑外侧与参与处理时间信息的其他大脑区域（例如前额叶皮层）密切相关。这些通路为小脑参与涉及时间信息处理的网络提供了基础；然而，人们对从小脑传递到该网络其他部分的信息知之甚少。拟议的实验旨在研究小脑-前额皮质回路在计时行为中的功能，为理解小脑损伤如何导致认知缺陷提供基础。小脑被认为对于时间处理至关重要，特别是在短期内（<1）。第二）；然而，基于这种时间信息的决策需要前额叶皮层的参与，因此，必须有一个专门的系统涉及将这些信息从小脑转移到前额叶皮层。小脑编码有关刺激的时间信息，以及如何将这些信息传输到前额叶皮层以存储在工作记忆中并最终用于做出决策。此外，我们将研究持续的小脑输入对于所涉及的前额叶回路的正常运作是否是必要的。为了解决这些问题，我们将使用经过训练的啮齿动物来根据时间（持续时间）和非时间（例如音调）特征来区分刺激。第一个目标是光遗传学技术。将用于以精确定时的方式操纵离开小脑的实际信号（即齿状核细胞的活动），以研究对动物时间判断的影响。由此产生的行为改变应提供信息。关于小脑如何计算时间信息，何时将信息传输到前额叶皮层，以及小脑活动是否影响前额叶皮层的记忆过程在第二个目标中，我们将获得细胞外的记录。在执行研究小脑对时间信息的特定编码的任务期间齿状核神经元的活动，这些信息将显着提高我们对小脑和大脑如何相互作用以及小脑和前额皮质功能障碍如何导致的理解。各种神经和精神疾病。