Functions of Saccadic Circuits in Lateral Cerebellar Cortex

小脑外侧皮层扫视回路的功能

• 批准号: 8359944
• 负责人: Marc A Sommer
• 金额: $ 21.11万
• 依托单位: DUKE UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2012
• 资助国家: 美国
• 起止时间: 2012-09-01 至 2014-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8359944
• 关键词: Action Potentials; Affect; Anatomy; Animals; Area; Behavior; Behavioral; Brain; Cells; Cerebellar Diseases; Cerebellar cortex structure; Cerebellum; Cerebral cortex; Cerebrum; Cognition; Cognitive; Complex; Data; Dentate nucleus; Disease; Dorsal; Exhibits; Eye; Fiber; Foundations; Future; Goals; Golgi Apparatus; Histologic; Image; Indium; Inferior; Interneurons; Knowledge; Lateral; Lead; Lesion; Macaca; Magnetic Resonance Imaging; Maps; Mediating; Monkeys; Motor; Movement; Neuroanatomy; Neurons; Olives - dietary; Outcome; Output; Parietal; Pattern; Physiological; Play; Pontine structure; Primates; Process; Publishing; Purkinje Cells; Rest; Role; Saccades; Shapes; Side; Signal Transduction; Site; Structure; Structure-Activity Relationship; Surveys; Testing; Textbooks; Time; Tracer; Work; base; cell type; design; executive function; follow-up; granule cell; improved; inhibitory neuron; insight; kinematics; mossy fiber; motor control; motor learning; neuroimaging; neurophysiology; neuropsychiatry; novel; operation

DESCRIPTION (provided by applicant): The cerebellum is a crucial brain structure for the control of movement. Recent data from lesion studies, neuroimaging, and neuroanatomy also implicate its lateral portion in non-motor functions, including cognitive processes. The lateral cerebellum may participate in such functions through its closed-loop connections with prefrontal and parietal cerebral cortex. A critical segment of these loops involves circuitry within the laterl cerebellum itself, extending through its cortical mantle to the dentate nucleus. Essentially nothing is known about non-motor signals in these intracerebellar circuits. We will record the signals directly in macaque monkeys that perform tasks involving cognitive demands such as self-timing of behavior. The studies are challenging because the cerebellar cortex, even just its lateral portion, is vast. Moreover it is highly foliated and deep in the brain, making it difficultto survey neurophysiologically. Efficient and systematic neurophysiology can now be achieved, however, based on recently available neuroanatomical maps that detail the motor and non- motor domains of cerebellar cortex. Our first aim is to record from neurons in two restricted zones of lateral cerebellar cortex known to be functionally connected with prefrontal and parietal cerebral cortex. The recording zones will be targeted using structural MRIs of each monkey's cerebellum referenced to published connectivity maps. During recordings, we will use physiological criteria to identify signals conveyed at three functional levels: cerebellar cortical output (Purkinje cells), input (mossy and climbing fibers), and local processing (Golgi cells). Our second aim provides for a definitive follow-up by comparing our recording sites with histologically documented cerebellar circuits in the same animals. This anatomical conclusion is crucial for interpreting the results of the first aim and for informing the strategies of future studies. The end result of this project will be a systematic description of both the non-motor and motor information conveyed within physiologically identified, and anatomically confirmed, circuits of the lateral cerebellum. The broader outcomes will be to improve our understanding of how the cerebellum helps to mediate cognition and to provide a novel functional perspective on the relation between cerebellar dysfunction and neuropsychiatric disorders. PUBLIC HEALTH RELEVANCE: It is textbook knowledge that the cerebellum contributes to motor learning and coordination, but recent evidence from imaging, anatomy, and lesion studies implicate it, as well, in non-motor functions such as cognition. Our work will analyze the information conveyed within microcircuits of the cerebellum in monkeys that perform both motor and non-motor tasks. The results will provide a circuit-level description of cerebellar participatin in non-motor functions and new insights into the association between cerebellar dysfunction and neuropsychiatric disorders.

描述(申请人提供)：小脑是控制运动的关键大脑结构。来自损伤研究、神经成像和神经解剖学的最新数据也表明，它的外侧部分与非运动功能有关，包括认知过程。外侧小脑可能通过其与前额叶和顶叶大脑皮层的闭合环状连接参与这种功能。这些环路的一个关键部分涉及到外侧小脑自身内部的电路，通过其皮质外套膜延伸到齿状核。基本上，我们对这些小脑内回路中的非运动信号一无所知。我们将直接在猕猴身上记录这些信号，这些猕猴执行的任务涉及认知需求，如行为的自我计时。这些研究具有挑战性，因为小脑皮质，即使只是它的外侧部分，也是巨大的。此外，它高度分叶，位于大脑深处，因此很难对其进行神经生理学研究。然而，基于最近可用的神经解剖图，现在可以实现有效和系统的神经生理学，这些图详细描述了小脑皮质的运动和非运动领域。我们的第一个目标是从小脑外侧皮质的两个受限区域的神经元记录，这两个区域已知在功能上与前额叶和顶叶大脑皮质有关。记录区将根据公布的连接图，使用每只猴子小脑的结构磁共振成像进行定位。在录音过程中，我们将使用生理标准来识别在三个功能水平上传递的信号：小脑皮质 输出(浦肯野细胞)、输入(苔藓和攀援纤维)和局部处理(高尔基细胞)。我们的 第二个目的是通过将我们的记录地点与组织学记录的相同动物的小脑回路进行比较，提供明确的后续研究。这一解剖学结论对于解释第一个目标的结果和指导未来研究的策略至关重要。该项目的最终结果将是对在生理识别和解剖学确认的小脑外侧回路内传递的非运动和运动信息进行系统描述。更广泛的结果将是提高我们对小脑如何帮助调节认知的理解，并为小脑功能障碍和神经精神障碍之间的关系提供一个新的功能视角。 与公共健康相关：小脑有助于运动学习和协调，这是教科书上的知识，但来自成像、解剖学和损伤研究的最新证据表明，小脑也与认知等非运动功能有关。我们的工作将分析猴子小脑微电路中传递的信息，这些猴子既执行运动任务，也执行非运动任务。这一结果将提供对小脑参与非运动功能的电路水平的描述，并对小脑功能障碍和神经精神障碍之间的联系提供新的见解。