Structural Organization of the Superior Colliculus

描述（由申请人提供）：感觉和运动系统的整合可能是神经系统最基本的成就，也是神经生物学中广泛感兴趣的话题。这种整合的一个基本特征是神经系统能够区分有机体自身运动产生的感觉刺激和外部诱导的刺激。在这个应用中，提出了一个电路模型来解释在跳眼运动期间由视野的快速运动引起的视觉刺激是如何减弱的，以防止知觉模糊和触发不必要的后续跳眼。该模型假设位于上丘中间层的运动前细胞能够指挥扫视，产生局部轴突侧支，激活邻近的gaba能抑制神经元。该模型还假设这些中间层gaba能神经元抑制上丘浅层的视感觉神经元。本应用程序的目的是使用体外解剖和生理技术的结合来测试该模型。我们的第一个特定目标是确定投射到浅层的中间层gaba能细胞是否接受来自邻近前运动细胞的兴奋性输入。第二个特定目的是确定接受gaba能输入的浅层视觉感觉细胞是否会投射到底层的前运动细胞和视觉丘脑的丘脑皮质中继细胞。在扫视过程中，gaba能通路会减弱对运动前细胞和皮层视觉区域的输入。在GAD 67-GFP敲入小鼠中，浅层和中间层的神经元将通过GFP荧光或在其轴突目的地注射逆行示踪剂来识别。它们对突触前细胞的层内和层内光刺激的突触反应将通过全细胞膜片钳记录来测量。除了在细胞水平上测试视觉运动系统基本特性的电路模型外，这些实验将加深我们对上丘层内和层间电路的结构和功能的理解。了解正常的电路将使我们能够提出合理的假设来解释与疾病相关的功能失调的感觉运动行为。

DESCRIPTION (provided by applicant): The integration of sensory and motor systems is perhaps the most fundamental achievement of nervous systems and a topic of broad interest in neurobiology. One essential feature of this integration is the ability of nervous systems to distinguish the sensory stimulation generated by an organism's own movements from externally induced stimulation. In this application, a circuit model is proposed to explain how the visual stimulation resulting from the rapid movement of the visual field that occurs during a saccadic eye movement is attenuated to prevent both perceptual blurring and the triggering of unwanted subsequent saccades. The model hypothesizes premotor cells located in the intermediate layer of the superior colliculus that command saccades give rise to local axonal collaterals that activate neighboring GABAergic inhibitory neurons. The model also hypothesizes that these intermediate layer GABAergic neurons inhibit visuosensory neurons in the superficial layer of the superior colliculus. The goal of this application is to test this model using a combination of in vitro anatomical and physiological techniques. Our first Specific Aim is to determine whether the intermediate layer GABAergic cells that project to the superficial layer receive excitatory input from neighboring premotor cells. The second Specific Aim is to determine whether the visuosensory cells in the superficial layer that receive the GABAergic input project to the underlying premotor cells and to thalamocortical relay cells in the visual thalamus. During saccades, this GABAergic pathway would attenuate the inputs to both the premotor cells and the visual areas of the cortex. Neurons in the superficial and intermediate layers will be identified either by GFP fluorescence in GAD 67-GFP knock-in mice or with retrograde tracers injected in the destinations of their axons. Their synaptic responses to intra- and intralaminar photostimulation of presynaptic cells will be measured by whole-cell patch clamp recordings. In addition to testing at the cellular level a circuit model for a fundamental property of visuomotor systems, these experiments will deepen our understanding of the structure and functions of the intra- and interlaminar circuitry of the superior colliculus. Understanding the normal circuitry will allow us to develop rational hypotheses to explain dysfunctional sensorimotor behavior associated with disease.