Functions of Saccadic Circuits in Lateral Cerebellar Cortex

描述（由申请人提供）：小脑是控制运动的关键大脑结构。最近的损伤研究，神经影像学和神经解剖学的数据也暗示其外侧部分在非运动功能，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环连接参与这些功能。这些回路的一个关键部分涉及小脑外侧自身内的回路，该回路通过小脑皮质外套延伸到齿状核。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，猕猴执行的任务涉及认知需求，如自我计时的行为。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，它是高度叶状的，在大脑深处，使其难以调查神经生理学。然而，基于最近可用的详细描述小脑皮质运动和非运动域的神经解剖图，现在可以实现有效和系统的神经生理学。我们的第一个目标是记录已知与前额叶和顶叶大脑皮层功能相关的小脑外侧皮层两个限制区的神经元。将使用参考已发表的连接图的每只猴小脑的结构MRI靶向记录区。在记录过程中，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（苔藓纤维和攀缘纤维）和局部加工（高尔基细胞）。我们 第二个目的是通过比较我们的记录部位与相同动物的组织学记录的小脑回路来提供明确的随访。这一解剖结论对于解释第一个目标的结果和为未来研究的策略提供信息至关重要。这个项目的最终结果将是一个系统的描述内生理上确定的，并在解剖学上证实，小脑外侧回路的非运动和运动的信息。更广泛的结果将是提高我们对小脑如何帮助介导认知的理解，并为小脑功能障碍和神经精神疾病之间的关系提供一个新的功能视角。 公共卫生相关性：小脑有助于运动学习和协调，这是教科书上的知识，但最近来自成像，解剖学和病变研究的证据表明，它也参与了非运动功能，如认知。我们的工作将分析猴子小脑微电路内传递的信息，这些猴子同时执行运动和非运动任务。这些结果将为小脑参与非运动功能提供一个回路水平的描述，并为小脑功能障碍和神经精神疾病之间的关联提供新的见解。

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.