MIDBRAIN CIRCUITRY FOR NEURONAL CONTROL OF GAZE

描述（由申请人提供）：人类作为中心窝生物，通过一系列的目光变化，包括眼球跳动，在许多情况下，伴随着头部的快速运动，不断地检查他们的环境。正常的视觉知觉要求这些运动准确而精确地协调。因此，干扰凝视的神经系统疾病会使人非常虚弱，通常会产生导致初次临床访问的症状。我们的长期目标是分析凝视背后的神经回路。中脑网状结构（central mesphalic reticular formation, cMRF）是上丘（上丘）的主要中脑靶点，被认为除了对上丘进行反馈外，还向脑干视觉运动结构和脊髓提供输入。cMRF刺激引起凝视的变化，该区域包含几种不同的生理细胞类型，在跳眼运动之前激活。然而，我们对cMRF连接的了解是有限的。在这项研究中，将在猕猴身上进行一系列双示踪实验，以确定cMRF与延髓网状脊髓神经元、脊髓运动神经元、背前束突出的SCol神经元以及与旁脉桥网状形成（PPRF）的联系。这些投影将使用包埋后免疫组织化学进行测试，以确定它们是否具有gaba能（抑制性）。将利用多种荧光示踪剂注射来确定是否单独的神经元群向髓网状结构和颈髓中的SCol、PPRF和头部运动中心提供输入。此外，这些cMRF神经元将根据它们的丘输入来表征。双示踪实验的光学和电子显微镜分析将允许cMRF及其目标的输入/输出关系在神经元水平上被指定。这些实验的结果将验证cMRF为SCol提供单独通道来调节凝视的眼睛和头部成分的假设。此外，他们将在神经元水平上提供对cMRF和SCol电路的理解，这有助于描述当前和未来凝视产生模型的可行性。因此，本研究将为更好地理解凝视机制和病理提供科学依据。

DESCRIPTION (provided by applicant): Humans, as foveate creatures, continuously examine their environment through a series of gaze changes involving saccadic eye movements and, in many cases, quick accompanying head movements. Normal visual perception requires that these movements be accurate and precisely coordinated. Consequently, neurological disorders that interfere with gaze are quite debilitating, often producing symptoms that result in the initial clinical visit. Our long-term goal is to analyze the circuitry underlying gaze. The central mesencephalic reticular formation (cMRF) represents the major midbrain target of the superior colliculus (SCol), and is believed to provide input to brainstem visual motor structures, and the spinal cord, in addition to feeding back upon the SCoI. cMRF stimulation elicits gaze changes, and this region contains several different physiological cell types that fire before saccadic eye movements. However, our knowledge of cMRF connectivity is limited. In this study, a series of dual tracer experiments will be undertaken in macaque monkeys to define cMRF connections with reticulospinal neurons in the medulla, motoneurons in the spinal cord, SCol neurons projecting in the predorsal bundle, and with the paramedian pontine reticular formation (PPRF). These projections will be tested utilizing post-embedding immunohistochemistry to determine whether they are GABAergic (inhibitory). Multiple fluorescent tracer injections will be utilized to determine whether separate neuronal populations provide inputs to the SCol, PPRF, and head movement centers in the medulary reticular formation and cervical cord. In addition, these cMRF neurons will be characterized with respect to their collicular input. Light and electron microscopic analysis of the dual tracer experiments will allow input/output relationships in the cMRF and its targets to be specified at the neuronal level. The results from these experiments will test the hypothesis that the cMRF provides the SCol with separate channels to modulate the eye and head components of gaze. In addition, they will provide an understanding of the cMRF and SCol circuitry at the neuronal level that can help delineate the feasibility of current and future models of gaze generation. Thus, this study will provide a scientific basis for better understanding gaze mechanisms and pathology.