Neural circuitry of the parietal lobe

(修订摘要)描述这一试验性研究方案打破了30年来以顶下小叶单个神经元的特性为特征的概念，该特性具有日益复杂的行为任务和旨在分离特定认知功能的分析。最近的光学成像研究显示，在顶下小叶的皮质表面上存在多个不同的地形图。分辨率最低，也是最稳健的是轨道增益场的表示；在V1中，光流似乎表示在这个范围内，就像方向在视网膜复制范围内一样。该提案从一个新的角度--神经回路--研究了顶叶下部的这两种功能。在顶叶皮质中，根本没有直接证据来解释它的感觉和获得场神经元属性是如何产生的。单个神经元的分子遗传学将被修改，以测量选定神经元和神经元群体的活动。标准显微镜将用于人口测量。双光子扫描显微镜将用于直接比较细胞的形态和功能。将对特定神经元进行多天的鉴定和研究，以评估其性质的稳定性。这一概念和研究回路的技术对于联合皮质来说是完全新颖的；在行为动物体内使用改进的神经元分子遗传学还没有在任何皮质区域进行过。这些研究的影响将是打开行为动物的纹状体以外的皮质到电路水平的分析。原则上，成像的分辨率可以扩展到亚细胞元素的水平，如脊椎。总而言之，这一提议旨在了解顶下小叶神经元在潜在神经元回路方面的特性，就像研究人员现在正在成功探索初级视觉皮质中定向调节和颜色的回路细节一样。虽然技术和概念问题很困难，但汇集的专业知识适合这项任务。这些研究的成功结果将是一个实质性的进步，使人们能够直接看到顶下小叶最高水平认知功能(如注意力、记忆、意图和可塑性)背后的亚细胞、细胞和回路属性。

(Revised Abstract) DESCRIPTION This pilot research proposal is a conceptual break from a thirty year tradition characterizing the properties of single neurons in the inferior parietal lobule with increasingly complex behavioral tasks and analyses designed to isolate particular cognitive functions. Recent optical imaging studies have revealed the presence of multiple different topographic maps across the cortical surface of the inferior parietal lobule. The lowest resolution, and most robust is a representation of orbital gain fields; optic flow appears to be represented within this much as orientation is within retinotopy in V1. The proposal examines these two functions in inferior parietal lobe from a novel perspective- the neural circuit. There is simply no direct evidence in parietal cortex explaining how its sensory and gain field neuronal properties are generated. The molecular genetics of single neurons will be modified to measure the activity of selected neurons and populations of neurons. Standard microscopy will be used for population measures. Two-photon scanning microscopy will be use to directly compare cellular morphology and function. Specific neurons will be identified and studied over many days to assess the stability of their properties. This concept and the techniques for studying the circuitry is completely novel for association cortex; the use of modified molecular genetics of neurons in vivo in behaving animals has not been performed in any cortical area. The impact of these studies will be to open up cortex beyond striate in the behaving animal to circuit level analysis. In principle, the resolution of imaging can be extended to the level of the sub-cellular elements such as spines. In summary, this proposal is designed to understand properties of inferior parietal lobule neurons in terms of underlying neuronal circuits, much as investigators are now successfully exploring the circuit details of orientation tuning and color in primary visual cortex. Although the technical and conceptual issues are difficult, the expertise assembled is appropriate to the task. The successful outcome of these studies will be a substantial advance permitting direct visualization of the sub-cellular, cellular and circuit properties underlying the highest level cognitive functions such as attention, memory, intention and plasticity in the inferior parietal lobule.