Neural circuitry of the parietal lobe

这个试点研究计划是一个概念上的突破，打破了30年来的传统，描述了下顶叶中单个神经元的特性，这些神经元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，在顶叶下皮层表面存在多种不同的地形图。分辨率最低、鲁棒性最强的是轨道增益场的表示；视光流在这幅图中表现得就像V1中视网膜置换术中的定向一样。本文从一个新颖的视角——神经回路来考察下顶叶的这两种功能。在顶叶皮层中根本没有直接的证据来解释它的感觉和增益场神经元特性是如何产生的。单个神经元的分子遗传学将被修改，以测量选定的神经元和神经元群体的活动。标准显微镜将用于种群测量。双光子扫描显微镜将用于直接比较细胞形态和功能。特定的神经元将被识别和研究许多天，以评估其特性的稳定性。这种研究回路的概念和技术对联想皮层来说是全新的；在行为动物体内使用改良的神经元分子遗传学尚未在任何皮质区域进行。这些研究的影响将是将行为动物的皮层从纹状体扩展到回路水平的分析。原则上，成像的分辨率可以扩展到亚细胞元素的水平，如脊柱。综上所述，本研究旨在从底层神经元回路的角度理解下顶叶神经元的特性，就像研究人员现在成功地探索初级视觉皮层中定向调谐和颜色的回路细节一样。虽然技术和概念问题是困难的，但汇集的专门知识是适合这项任务的。这些研究的成功结果将是一个实质性的进步，允许直接可视化亚细胞、细胞和电路特性，这些特性隐藏在最高水平的认知功能中，如顶叶下的注意力、记忆、意图和可塑性。

(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.