Structural Organization of the Superior Colliculus

描述（由申请人提供）：神经生物学的一个巨大挑战是理解感觉和运动系统是如何结合在一起产生行为的。同时具有感觉和运动特性的细胞使上丘成为研究这一过程的有效模型。通过应用研究上丘的新方法，包括体外全细胞膜片钳记录和光刺激，我们首次在细胞水平上分析了连接其感觉和运动功能的内在电路。通过在记录期间用神经元示踪剂填充细胞，并用逆行运输的示踪剂预先标记细胞，它们的生理学与它们的形态和连接相关。使用这种方法，我们证明了编码视觉刺激位置的浅丘层将兴奋信号发送到更深层的前运动细胞，后者生成视觉引导的注视方向移动命令。运动前皮层也接受来自脑干细胞的密集胆碱能输入，这些脑干细胞调节通过丘脑视觉部分到皮层的感觉信息流。我们的第一个具体目标是测试这样一种观点，即这种胆碱能输入协调了传递到皮层的感觉信号的增强，并开始了针对视觉刺激的定向运动。我们的第二个特定目标是测试通过远程抑制来调节前运动活动的观点——在左右丘之间，在吻侧注视和尾侧注视转移神经元之间——允许前运动细胞的激活，这些细胞指挥头部和眼睛朝着一个方向的视觉刺激运动，同时减弱前运动细胞的活动，这些细胞会向其他方向的刺激控制竞争运动。这些实验将有助于我们了解正常和患病大脑的感觉运动功能

DESCRIPTION (provided by applicant): One of the great challenges in neurobiology is to understand how sensory and motor systems are integrated to produce behavior. The juxtaposition of cells with sensory and motor properties has made the superior colliculus a fruitful model for studying this process. By applying methods new to the study of the superior colliculus, including in vitro whole-cell patch-clamp recording and photostimulation, we are analyzing for the first time at the cellular level the intrinsic circuitry that links its sensory and motor functions. By filling the cells during recording with neuronal tracers and by pre-labeling them with retrogradely transported tracers, their physiology is correlated with their morphology and connections. Using this approach, we demonstrated that the superficial collicular layer, which encodes the location of visual stimuli, sends excitatory signals to a deeper layer of premotor cells, which generates commands for visually guided shifts in the direction of gaze. The premotor layer also receives a dense cholinergic input that arises from the same brainstem cells that modulate the flow of sensory information through the visual part of the thalamus to the cortex. Our first Specific Aim is to test the idea that this cholinergic input coordinates the enhancement of sensory signals transmitted to the cortex with the initiation of orienting movements toward visual stimuli. Our second Specific Aim is to test the idea that modulation of premotor activity by long-range inhibition - between the right and left colliculi and between rostral fixation and caudal gaze shifting neurons - permits the activation of premotor cells that command head and eye movements toward visual stimuli in one direction while attenuating the activity of premotor cells that would command competing movements toward stimuli in other directions. These experiments will contribute to our understanding of sensorimotor functions in the normal and diseased brain