MIDBRAIN CIRCUITRY FOR NEURONAL CONTROL OF GAZE

用于注视神经元控制的中脑电路

• 批准号: 6861719
• 负责人: Paul J May
• 金额: $ 29.6万
• 依托单位: UNIVERSITY OF MISSISSIPPI MED CTR
• 依托单位国家: 美国
• 财政年份: 2003
• 资助国家: 美国
• 起止时间: 2003-04-01 至 2007-02-28
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6861719
• 关键词: Macaca; behavioral /social science research tag; brain stem; electron microscopy; fluorescent dye /probe; head movements; immunocytochemistry; light microscopy; mesencephalon; motor neurons; neural information processing; neuroanatomy; neurons; neuroregulation; reticular formation; saccades; smooth pursuit eye movement; superior colliculus; synapses; tegmentum; visual feedback; visual fixation; visual perception

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.

描述(申请人提供)：人类，作为凹陷生物，通过一系列的凝视变化来持续检查他们的环境，包括眼跳运动，在许多情况下，伴随着快速的头部运动。正常的视觉感知要求这些动作准确和精确地协调。因此，干扰凝视的神经障碍相当虚弱，通常会产生导致最初临床就诊的症状。我们的长期目标是分析凝视背后的回路。中央中脑网状结构(CMRF)是上丘(SCOL)的主要中脑靶点，被认为除了对SCOI进行反馈外，还为脑干视觉运动结构和脊髓提供输入。CMRF刺激引起凝视变化，这一区域包含几种不同类型的生理细胞，它们在眼球跳动之前被激发。然而，我们对CMRF连接性的了解是有限的。在这项研究中，将在猕猴身上进行一系列的双重示踪实验，以确定cMRF与延髓中的网状脊髓神经元、脊髓中的运动神经元、投射在背前束中的SCOL神经元以及与桥旁网状结构(PPRF)的联系。这些投射将利用包埋后免疫组织化学进行测试，以确定它们是否为GABA能(抑制性)。多次荧光示踪剂注射将被用来确定单独的神经元群体是否向延髓网状结构和颈髓的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脑输入进行特征描述。对双示踪剂实验的光学和电子显微镜分析将允许在神经元水平上指定cMRF及其靶点的输入/输出关系。这些实验的结果将检验这样一种假设，即cMRF为SCOL提供了单独的通道来调节凝视的眼睛和头部成分。此外，他们还将在神经元水平上提供对cMRF和SCOL电路的理解，这有助于描绘当前和未来凝视生成模型的可行性。因此，本研究将为更好地理解凝视机制和病理学提供科学依据。