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Role of inhibitory interneurons in generating febrile seizures

抑制性中间神经元在热性惊厥发生中的作用

基本信息

批准号：
7486546
负责人：
Jennifer A Kim
金额：
$ 3.59万
依托单位：
BROWN UNIVERSITY
依托单位国家：
美国
项目类别：
财政年份：
2008
资助国家：
美国
起止时间：
2008-04-01 至 2014-03-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/7486546
关键词：
Action Potentials Acute Address Adolescent Adult Animal Model Brain Cells Characteristics Condition Convulsions Development Epilepsy Evoked Potentials Excitatory Synapse Febrile Convulsions Fever Fire - disasters Generations Grant High temperature of physical object Hippocampus (Brain)Hyperventilation In Vitro Interneurons Knock-out Limbic System Link Localized Location Measures Membrane Methods Mission Modification Neocortex Neurons Play Population Preparation Property Prophylactic treatment Rate Receptor Activation Resistance Respiratory Alkalosis Role Seizures Site Slice Stimulus Synapses TRPV1 gene Temperature Temporal Lobe Epilepsy Testing Time Whole-Cell Recordings Wild Type Mouse Work afterpotential early childhood experience extracellular falls hippocampal pyramidal neuron in vivo infancy insight nervous system disorder neuronal excitability postsynaptic receptor voltage

项目摘要

DESCRIPTION (provided by applicant): Seizures are sudden attacks or convulsions due to abnormal, hypersynchronous discharges from a population of neurons in the brain. Approximately 5-10% of people will experience one seizure in their lifetime. Febrile seizures are the most common cause of seizures in late infancy and early childhood. Though this type of seizure is prevalent throughout the world, very little is known about its mechanisms. A recent study suggested that fever induces hyperventilation and respiratory alkalosis, and that an increase in brain pH may be the proximate cause of febrile seizures. In my proposed project, I plan to test the hypothesis that temperature- and pH-induced changes of inhibitory circuits contribute to the generation of febrile seizures. First, I will examine how spontaneous and evoked extracellular field potentials in the CA1 field of the hippocampus change under conditions of high temperature and high pH. These results will allow me to determine whether high temperature, high pH or the combination of both increase hyperexcitability. Second, I will use whole-cell patch recording methods to evaluate whether temperature or pH changes alter the intrinsic membrane excitability and synaptic connections of two specific types of inhibitory interneurons or pyramidal neurons. I will use whole-cell recordings from pairs of identified interneurons or from interneuronpyramidal cell pairs. I will use small hyperpolarizing and depolarizing current steps to measure both subthreshold and active properties of each cell. I will measure changes in spontaneous synaptic activity and specific excitatory and inhibitory synaptic connections. I will correlate changes in synaptic and intrinsic properties of inhibitory interneurons with the onset of epileptiform activity in local networks. Third, I will investigate the potential role of temperature- and pH-sensitive transient receptor potential vallinoid receptor 1 (TRPV1 receptor) activation in increasing neuronal excitability during high temperature and/or pH conditions by comparing TRPV1 knockout to wild-type mice. Both in vivo and in vitro methods will be used to fully evaluate the potential effects of TRPV1 receptors. My results should contribute significantly to our understanding of the basic mechanisms of febrile seizures. With better insight into the causes of febrile seizures, we may be able to optimize prophylaxis and treatment. This work would contribute directly to the mission of NINDS to reduce the burden of neurological disease.

描述（由申请人提供）：