A new model of the role of the basal ganglia in eye movement initiation.

基底神经节在眼球运动启动中的作用的新模型。

• 批准号: 8776716
• 负责人: Michele A Basso
• 金额: $ 19.42万
• 依托单位: UNIVERSITY OF CALIFORNIA LOS ANGELES
• 依托单位国家: 美国
• 财政年份: 2013
• 资助国家: 美国
• 起止时间: 2013-12-01 至 2016-11-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8776716
• 关键词: Action Potentials; Attention Deficit Disorder; Basal Ganglia; Behavior; Birds; Brain; Brain Stem; Cations; Cell Nucleus; Cerebral cortex; Cerebrum; Complex; Decision Making; Disease; Disinhibition; Eye Movements; Generations; Gilles de la Tourette syndrome; Globus Pallidus; Glutamates; Goals; Health; Huntington Disease; In Vitro; Interneurons; Label; Location; Mediating; Membrane; Methodology; Midbrain structure; Modeling; Movement; Movement Disorders; Mus; Neurologic; Neurons; Obsessive-Compulsive Disorder; Output; Parkinson Disease; Pathway interactions; Pattern; Play; Pontine structure; Process; Property; Regulation; Research; Rodent Model; Role; Saccades; Schizophrenia; Series; Signal Transduction; Slice; Source; Structure; Substantia nigra structure; Symptoms; Synapses; System; Testing; Textbooks; Thalamic structure; Training; Vertebrates; Vision; Visual; Visual Fields; Work; base; cell type; excitatory neuron; gaze; neuropsychiatry; oculomotor; programs; putamen; rapid eye movement; receptor; research study; role model; superior colliculus Corpora quadrigemina; visual process; visual processing; voltage; voltage clamp

DESCRIPTION: In this application we have one Specific Aim: To test a new model of saccade generation by the nigro-colliculus pathway by determining the influence of the inhibitory inputs from the substantia nigra pars reticulata (nigra) on identified neuronal cell types within the superior colliculus. To achieve this aim we propose two experiments using the in vitro rodent model. Each of these experiments will be performed on both projection neurons and GAD 67 GFP labeled interneurons within both the intermediate (premotor) layers and the superficial (visual) layers of the colliculus. We shall, 1) introduce hyperpolarizing current into collicular neurons to assess expression of Ih, the hyperpolarization activated cation current and use hyperpolarizing voltage steps under voltage clamp to test for Ih in collicular neurons. 2) Introduce realistic spike trains into the nigra and record from neurons in the colliculus to assess whether nigral activity invokes Ih leading to bursting in superior colliculus neurons. The work proposed here may change the current dogma regarding the role of the nigro-collicular pathway in eye movement initiation by showing that its role is active rather than a passive gating of cortical afferents. The results therefore, may provide a new understanding of how eye movement symptoms occurring in neurological and neuropsychiatric diseases involving the basal ganglia such as Parkinson's disease, Huntington's disease, Tourette syndrome, attention deficit disorder, obsessive compulsive disorder and schizophrenia arise.

描述：在此应用中，我们有一个具体目标：通过确定黑质网状部 (nigra) 的抑制输入对上丘内已识别的神经元细胞类型的影响，测试黑丘通路产生眼跳的新模型。为了实现这一目标，我们提出了使用体外啮齿动物模型的两个实验。这些实验中的每一个都将在丘的中间（前运动）层和表面（视觉）层内的投射神经元和 GAD 67 GFP 标记的中间神经元上进行。我们应该，1）将超极化电流引入丘脑神经元以评估Ih（超极化激活的阳离子电流）的表达，并在电压钳下使用超极化电压阶跃来测试丘脑神经元中的Ih。 2) 将真实的尖峰序列引入黑质并记录丘中神经元的数据以进行评估 黑质活动是否会引发 Ih 导致上丘神经元爆发。这里提出的工作可能会改变当前关于黑质丘脑通路在眼球运动启动中的作用的教条，表明其作用是主动的，而不是皮质传入的被动门控。因此，这些结果可能为涉及基底神经节的神经和神经精神疾病（如帕金森病、亨廷顿病、抽动秽语综合征、注意力缺陷障碍、强迫症和精神分裂症）中出现的眼动症状提供新的认识。