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

产品说明：在本申请中，我们有一个具体的目的：通过确定黑质网状部（黑质）的抑制性输入对上级丘内已识别的神经元细胞类型的影响，来测试黑质-丘通路产生扫视的新模型。为了实现这一目标，我们提出了两个实验，在体外啮齿动物模型。这些实验中的每一个都将在丘的中间（运动前）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。我们将1）在丘神经元中引入超极化电流以评估Ih的表达，超极化激活的阳离子电流，并在电压钳下使用超极化电压阶跃来测试丘神经元中的Ih。2)将真实的尖峰序列引入黑质，并记录丘神经元的记录， 黑质活性是否引起Ih导致上级丘神经元的爆发。这里提出的工作可能会改变目前的教条，黑丘通路的作用，在眼动启动显示其作用是主动的，而不是被动的门控皮层传入。因此，这些结果可能会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）的眼动症状如何出现提供新的理解。

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.