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Testing the Excitability of Inhibitory Neurons

测试抑制性神经元的兴奋性

基本信息

批准号：
8441036
负责人：
JOSHUA G CORBIN
金额：
$ 18.57万
依托单位：
CHILDREN'S RESEARCH INSTITUTE
依托单位国家：
美国
项目类别：
财政年份：
2005
资助国家：
美国
起止时间：
2005-12-01 至 2012-08-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/8441036
关键词：
Affect Agonist Anxiety Area Autistic Disorder Characteristics Childhood Cognitive Cognitive deficits Communication Comorbidity Data Defect Development Disease Down-Regulation Endocannabinoids Epilepsy Exhibits Fragile X Syndrome Frequencies Functional disorder Genetic Glutamates Goals Hypersensitivity Impaired cognition Incidence Interneuron function Interneurons Knockout Mice Knowledge Lead Mental Retardation Messenger RNA Metabotropic Glutamate Receptors Mus Mutant Strains Mice Neurodevelopmental Disorder Output Pathologic Pathway interactions Patients Phenotype Process Proteins Pyramidal Cells Receptor Signaling Regulation Rodent Role Seizures Sensory Sensory Process Signal Pathway Signal Transduction Somatosensory Cortex Somatostatin Structure Synapses Testing Thalamic structure Therapeutic Work barrel cortex base design developmental disease inhibitory neuron interdisciplinary approach metabotropic glutamate receptor type 1 mouse model nervous system disorder network dysfunction neurotransmission neurotransmitter release novel promoter receptor receptor-mediated signaling research study sensory stimulus social somatosensory stem theories transmission process

项目摘要

DESCRIPTION (provided by applicant): Neurological disorders such as epilepsy and Fragile X Syndrome (FXS) are characterized with imbalances in excitatory and inhibitory neurotransmission. Patients with FXS exhibit a hyperexcitable phenotype evidenced by severe cognitive deficits, increased incidence of recurring seizures, social anxiety and hypersensitivity to sensory stimuli. We hypothesize that defects in inhibitory neurotransmission in primary somatosensory cortex underlie aspects of the hyperexcitable phenotype of FXS, including its comorbidity with epilepsy. In this project, we use a multidisciplinary approach combining electrophysiological and anatomical analyses with mouse genetic rescues to study the Fragile X phenotype in a cortical area relevant for both cognitive and sensory dysfunction. Our primary goals are to determine the mechanism of synaptic and network dysfunction in FXS. We will examine inhibitory neuron dysfunction through the view of two complementary theories that are hypothesized to lead to the hyperexcitable phenotype observed in FXS. We will additionally test whether altered excitability in inhibitory circuits can be rescued genetically in FXS mutant mice.

描述（由申请人提供）：神经系统疾病如癫痫和脆性X综合征（FXS）的特征是兴奋性和抑制性神经传递失衡。FXS患者表现出过度兴奋表型，表现为严重的认知缺陷、复发性癫痫发作的发生率增加、社交焦虑和对感觉刺激的超敏反应。我们推测，缺陷的抑制性神经传递在初级躯体感觉皮层的基础方面的过度兴奋表型的FXS，包括其合并症与癫痫。在这个项目中，我们使用一个多学科的方法相结合的电生理和解剖分析与小鼠遗传救援研究脆性X表型在相关的认知和感觉功能障碍的皮质区。我们的主要目标是确定FXS中突触和网络功能障碍的机制。我们将通过两种互补的理论来研究抑制性神经元功能障碍，这两种理论被假设为导致在FXS中观察到的过度兴奋表型。我们还将测试抑制回路中的兴奋性改变是否可以在FXS突变小鼠中通过遗传学方法挽救。