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（由申请人提供）：小脑是控制运动的重要大脑结构。来自病变研究、神经影像学和神经解剖学的最新数据也表明其外侧部分与非运动功能（包括认知过程）有关。小脑外侧可能通过其与前额叶和顶叶大脑皮层的闭环连接参与这些功能。这些环路的一个关键部分涉及小脑外侧本身的电路，通过其皮质套延伸到齿状核。基本上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信号，这些猕猴执行涉及认知需求的任务，例如行为的自我计时。这些研究具有挑战性，因为小脑皮层，即使只是其外侧部分，也是巨大的。此外，它的叶状结构丰富，位于大脑深处，因此很难从神经生理学角度进行研究。然而，基于最近可用的详细描述小脑皮层运动和非运动域的神经解剖图，现在可以实现高效和系统的神经生理学。我们的第一个目标是记录小脑外侧皮层两个限制区域中的神经元，这些区域已知与前额叶和顶叶大脑皮层有功能连接。将参考已发布的连接图，使用每只猴子小脑的结构核磁共振成像来定位记录区域。在录音过程中，我们将使用生理标准来识别在三个功能层面上传递的信号：小脑皮质 输出（浦肯野细胞）、输入（苔藓和攀缘纤维）和局部处理（高尔基细胞）。我们的 第二个目标是通过将我们的记录位点与同一动物的组织学记录的小脑回路进行比较，提供明确的后续行动。这一解剖学结论对于解释第一个目标的结果和为未来的研究策略提供信息至关重要。该项目的最终结果将是对在生理学上识别和解剖学上确认的外侧小脑回路中传递的非运动和运动信息的系统描述。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疾病之间的关系提供新的功能视角。 公共健康相关性：教科书上的知识是，小脑有助于运动学习和协调，但最近来自影像学、解剖学和病变研究的证据表明，小脑也与认知等非运动功能有关。我们的工作将分析执行运动和非运动任务的猴子小脑微电路内传递的信息。研究结果将为小脑参与非运动功能提供回路水平的描述，并为小脑功能障碍与神经精神疾病之间的关联提供新的见解。