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

在这个应用中，我们有一个特定的目的：通过确定来自黑质网状部（黑质）的抑制性输入对上丘内已识别的神经元细胞类型的影响，来测试一种由黑丘途径产生眼跳的新模型。为了实现这一目标，我们提出了两个实验使用体外啮齿动物模型。这些实验将在丘丘的中间层（运动前）和浅层（视觉）内的投射神经元和GAD 67 GFP标记的中间神经元上进行。我们将：1)引入超极化电流来评估超极化激活阳离子电流Ih的表达，并在电压箝位下使用超极化电压阶跃来检测细胞内Ih的表达。2)将真实的尖峰序列引入黑质，并从丘神经元中记录以评估

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.