Local Connections and in Vivo Physiology of Inhibitory Cortical Neurons.

抑制性皮质神经元的局部连接和体内生理学。

基本信息

批准号：
7833395
负责人：
XIANGMIN XU
金额：
$ 32.81万
依托单位：
UNIVERSITY OF CALIFORNIA-IRVINE
依托单位国家：
美国
项目类别：
财政年份：
2009
资助国家：
美国
起止时间：
2009-09-30 至 2011-09-29
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/7833395
关键词：
Area Award Behavior Biological Assay Brain Cells Cerebral cortex Cocaine Computer software DRD2 gene Data Development Disease model Dopamine Dopamine D1 Receptor Dopamine D2 Receptor Dopamine Receptor Drug Addiction Dyes Electric Stimulation Electrodes Embryo Equipment Evaluation Functional Imaging Funding Glutamates Health Human Image Imaging Techniques In Vitro Injection of therapeutic agent Interneurons Knock-out Knockout Mice Knowledge Lasers Life Link Maps Measurement Mediating Minority Morphology Mus Mutant Strains Mice Neurons Optics Output Pathway interactions Pattern Physiology Population Population Dynamics Preparation Property Radial Receptor Activation Recovery Regulation Reporting Research Research Personnel Resolution Rest Scanning Seizures Slice Source Specificity Speed Staining method Stains Structure Synapses System Techniques Technology Tissues Training Transgenic Mice United States National Institutes of Health Use of New Techniques Whole-Cell Recordings addiction cell type design graduate student improved in vitro activity in vivo information processing inhibitory neuron innovation migration novel photoactivation postsynaptic public health relevance receptor research study response spatiotemporal tool voltage

项目摘要

DESCRIPTION (provided by applicant): This is a competitive revision application for my NIH Pathway to Independence Award (4 R00DA023700) tilted "Local Connections and In Vivo Physiology of Inhibitory Cortical Neurons", in response to the NIH funding notice (NOT-OD-09-058, NIH Announces the Availability of Recovery Act Funds for Competitive Revision Applications). Despite extensive knowledge of the basic blueprint of cortical circuits, detailed knowledge about local cortical circuits, the connectivity of specific cell types and how they function is still limited. The studies originally proposed investigate the laminar and fine-scale specificities of excitatory and inhibitory synaptic input to specific types of inhibitory neurons in the cerebral cortex, and examine in vivo physiology of distinct inhibitory cell types and their participation and regulation of cortical activities. We have accomplished the aims of examining the laminar specificity of functional input to distinct cell types by combining whole cell recordings with scanning laser photostimulation in brain slices. We also have progressed toward understanding in vivo physiology of specific inhibitory cell types. Recently, we have developed a technique enabling high-resolution and fast functional imaging in brain slices through a novel combination of voltage sensitive dye imaging and laser scanning photostimulation. This innovation will have broad impacts in the field of cortical circuitry studies, as it facilitates rapid mapping and precise evaluation of cortical organization and function. The innovation will enable the ability to map inhibition output from inhibitory cell types by examining their influence on neuronal population activities evoked by photostimulation and detected by voltage sensitive dye imaging. Given the exciting developments of my original projects, I would like to revise my original aims, and focus on further improving the new technique and extending such technology toward elucidating cortical circuitry. The newly revised Specific Aims are to (1) Refine and improve the high-resolution and fast functional imaging technique in brain slices; (2) Map inhibitory output of specific types of inhibitory neurons using the novel technique; (3) Characterize circuit alterations in dopamine receptor knockout (D2R-/-) mice with the novel technique. This revision requests support to purchase additional equipment and train one minority graduate student. PUBLIC HEALTH RELEVANCE: Studies of the detailed organization of cortical circuits involving specific inhibitory cell types are necessary toward understanding cortical function. These studies have important implications for human health, as these cell types and their activities are involved in many disease models and can mediate the cortical mechanisms related to drug addiction and abuse.

描述（由申请人提供）：这是我的 NIH 独立之路奖（4 R00DA023700）的竞争性修订申请，倾斜“抑制性皮质神经元的局部连接和体内生理学”，以响应 NIH 资助通知（NOT-OD- 09-058，NIH 宣布恢复法案基金可用于竞争性修订申请）。尽管人们对皮质回路的基本蓝图有了广泛的了解，但有关局部皮质回路、特定细胞类型的连接性及其功能的详细知识仍然有限。这些研究最初提出研究大脑皮层中特定类型的抑制性神经元的兴奋性和抑制性突触输入的层状和精细尺度特异性，并检查不同抑制性细胞类型的体内生理学及其对皮质活动的参与和调节。通过将全细胞记录与脑切片中的扫描激光光刺激相结合，我们已经实现了检查不同细胞类型的功能输入的层特异性的目标。我们还在了解特定抑制细胞类型的体内生理学方面取得了进展。最近，我们开发了一种通过电压敏感染料成像和激光扫描光刺激的新颖组合在脑切片中实现高分辨率和快速功能成像的技术。这项创新将在皮质电路研究领域产生广泛影响，因为它有助于快速绘制和精确评估皮质组织和功能。这项创新将能够通过检查抑制细胞类型对光刺激引起的神经元群活动的影响并通过电压敏感染料成像检测来绘制抑制输出。鉴于我最初的项目取得了令人兴奋的进展，我想修改我最初的目标，并专注于进一步改进新技术并将此类技术扩展到阐明皮层电路。新修订的具体目标是：（1）细化和提高脑切片高分辨率、快速功能成像技术；（2）利用新技术绘制特定类型抑制性神经元的抑制输出图； (3) 利用新技术表征多巴胺受体敲除 (D2R-/-) 小鼠的电路变化。此修订要求支持购买额外设备并培训一名少数族裔研究生。公共健康相关性：对涉及特定抑制细胞类型的皮质回路的详细组织的研究对于了解皮质功能是必要的。这些研究对人类健康具有重要意义，因为这些细胞类型及其活动涉及许多疾病模型，并且可以介导与药物成瘾和滥用相关的皮质机制。