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：在这项应用中，我们有一个特定的目标：通过确定来自黑质网状部的抑制性输入对上丘内已识别的神经细胞类型的影响，测试黑质-丘脑通路产生眼跳的新模型。为了实现这一目标，我们提出了两个使用体外啮齿动物模型的实验。每个实验都将在投射神经元和GAD 67 GFP标记的中间神经元上进行，这些中间神经元位于丘脑的中间(运动前)层和浅(视觉)层。我们将：1)在丘脑神经元中引入超极化电流来检测超极化激活的阳离子电流Ih的表达，并在电压钳下用超极化电压阶跃来检测Ih的表达。2)将真实的棘波序列引入黑质，并记录小丘神经元以评估 黑质活动是否引起上丘神经元爆裂。本文提出的这项工作可能会改变目前关于黑丘通路在眼动启动中的作用的教条，表明它的作用是主动的，而不是皮层传入的被动门控。因此，这一结果可能对帕金森氏病、亨廷顿病、多发性抽动症、注意力缺陷障碍、强迫症和精神分裂症等涉及基底节的神经和神经精神疾病中眼动症状的产生提供新的理解。