Function of Neocortical GABAergic Interneurons in Local Circuit Activations

新皮质 GABA 能中间神经元在局部回路激活中的功能

• 批准号: 8132306
• 负责人: Tanya Sippy
• 金额: $ 4.06万
• 依托单位: COLUMBIA UNIV NEW YORK MORNINGSIDE
• 依托单位国家: 美国
• 财政年份: 2008
• 资助国家: 美国
• 起止时间: 2008-09-01 至 2012-05-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8132306
• 关键词: Ablation; Action Potentials; Address; Affect; Area; Biological; Biological Models; Brain; Cells; Complex; Cortical Column; Disease; Epilepsy; Event; Experimental Models; Fire - disasters; Frequencies; Interneuron function; Interneurons; Label; Laboratories; Lasers; Light; Link; Methods; Motor output; Mus; Neocortex; Neurons; Neurophysiology - biologic function; Neurotransmitters; Optics; Output; Pathology; Pattern; Play; Population; Property; Role; Schizophrenia; Sensory; Shapes; Slice; Somatosensory Cortex; Stereotyping; Stimulus; Techniques; Testing; Thalamic structure; Time; Training; Transgenic Mice; Work; base; hippocampal pyramidal neuron; in vivo; information processing; inhibitory neuron; insight; millisecond; neocortical; nervous system disorder; neural circuit; neural information processing; patch clamp; public health relevance; relating to nervous system; research study; response; spatiotemporal; stereotypy; two-photon

DESCRIPTION (provided by applicant): GABAergic interneurons, which are implicated in many disease states, form a small but crucial population of cortical neurons. Attempts to classify the vast array of interneurons in mammalian cortex have shed light on many of their basic properties, but very little is known about the function of distinct classes of interneurons in neuronal networks. While it has been shown GABAergic interneurons can affect the function of large brain areas, it is not known how they do so. The studies proposed here are aimed at elucidating the function of neocortical interneurons within the context of circuit activations. These activations, during which neurons are synchronously depolarized and fire action potentials, show spatio-temporal stereotypy and have been associated with important neural functions. GABAergic interneurons, which are thought to be important for controlling the output of excitatory cells, participate during circuit activations, but their exact role is unknown. This application, using cutting edge optical techniques, will focus on investigating how interneurons affect neuronal activity in local circuits. Specifically I will test the hypothesis that specific subclasses of interneurons are crucial for determining distinct features of cortical circuit activations. Using transgenic mouse lines in which subsets of GABAergic interneurons are labeled with GFP, I will decrease or increase the activity of target interneurons using three approaches: 1) whole cell patch clamping, 2) two photon laser ablation and 3) one/two photon uncaging of either excitatory or inhibitory neurotransmitters. PUBLIC HEALTH RELEVANCE: Since altered function of inhibitory neurons is thought to underlie a number of neurological disorders, including schizophrenia and epilepsy, the changes I observe in circuit activations may reflect the underlying network pathologies associated with these conditions.

描述（由申请人提供）： GABA能中间神经元与许多疾病状态有关，形成了少量但至关重要的皮质神经元。试图对哺乳动物皮质中大量的中间神经元进行分类的尝试已经揭示了其许多基本特性，但是对于神经元网络中不同类别的中间神经元的功能知之甚少。尽管已显示GABA能中间神经元可以影响大脑区域的功能，但尚不知道它们是如何做到的。此处提出的研究旨在阐明在电路激活背景下新皮质中间神经元的功能。这些激活在其同步去极化和火力作用电位的过程中显示出时空的定型观念，并与重要的神经功能有关。被认为对于控制兴奋性细胞的输出很重要的GABA能中间神经元在电路激活过程中参与其中，但其确切的作用尚不清楚。该应用使用尖端光学技术，将重点研究中间神经元如何影响局部电路中的神经元活动。具体而言，我将检验以下假设：中间神经元的特定亚类对于确定皮质电路激活的不同特征至关重要。使用转基因小鼠线，其中GABA能中间神经元的子集用GFP标记，我将使用三种方法降低或增加靶神经元的活性：1）全细胞贴剂夹紧，2）两个光子激光烧蚀和3）一个/两个光子在兴奋性或抑制性神经抑制性神经释放剂的启用。 公共卫生相关性：由于抑制性神经元的功能的改变被认为是许多神经系统疾病的基础，包括精神分裂症和癫痫病，因此我在电路激活中观察到的变化可能反映了与这些疾病相关的潜在网络病理。