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Kainate Receptors in Signaling Between Hippocampal Mossy Cells and Granule Cells

海马苔藓细胞和颗粒细胞之间信号传导中的红藻氨酸受体

基本信息

批准号：
8807381
负责人：
GEOFFREY T SWANSON
金额：
$ 23.18万
依托单位：
NORTHWESTERN UNIVERSITY AT CHICAGO
依托单位国家：
美国
项目类别：
财政年份：
2014
资助国家：
美国
起止时间：
2014-09-01 至 2016-08-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/8807381
关键词：
AMPA Receptors Animal Model Anticonvulsants Appearance Architecture Axon Brain Brain Injuries C57BL/6N Mouse Cells Chronic Communication Contralateral Data Dendrites Dendritic Spines Disease model Epilepsy Equilibrium Excitatory Synapse Feedback Future Gene Targeting Hilar Hippocampus (Brain)Human Interneurons Ipsilateral Kainic Acid Kainic Acid Receptors Mediating Modeling Mus Mutant Strains Mice Neurons Pathway interactions Pattern Perforant Pathway Physiological Pilocarpine Play Population Presynaptic Terminals Process Property Proteins Pyramidal Cells Regulation Rodent Rodent Model Role Seizures Signal Transduction Signaling Protein Slice Structure of molecular layer of cerebellar cortex Synapses Synaptic plasticity Temporal Lobe Epilepsy Time dentate gyrus granule cell hippocampal pyramidal neuron information processing memory process mossy fiber mouse model neuronal excitability novel optogenetics postsynaptic presynaptic public health relevance receptor receptor function selective expression synaptic function tool transmission process

项目摘要

DESCRIPTION (provided by applicant): Mossy cells in the hilar region are important but relatively understudied contributors to integration of cortical input to the hippocampus. Signaling mechanisms that impact mossy cell excitability and synaptic function are relevant to physiological network function, such as encoding of patterns of input, and play a role in pathological adaptations, as occur in epilepsy. Kainate receptors play important modulatory roles in network excitability elsewhere in the hippocampus through diverse functional activities that are neuron- and synapse-specific. How kainate receptors might contribute to excitatory signaling in hilar mossy cells and between mossy cells and either hilar interneurons or dentate granule cells is entirely unknown and is the focus of this project. We will determine if kainate receptors contribute to either efferent or afferent signaling in mossy cells. This objective is relevant to models of temporal lobe epilepsy because (i) mossy cells are central to the two predominant models of circuit hyperexcitability in chronic forms of temporal lobe epilepsy, and (ii) aberrant kainate receptor function was recently shown to contribute to seizures in rodent seizure models. In Specific Aim 1, we will determine the role and composition of kainate receptors in mossy cells, focusing particularly on postsynaptic kainate receptor function at granule cell - mossy cell synapses. The subunit composition of mossy cell kainate receptors will be determined using a combination of pharmacological tools and gene-targeted mice. In Specific Aim 2, we will examine potential contributions by kainate receptors to signaling between mossy cells and dentate granule cells or hilar interneurons. The architecture of mossy cell projections has made studying these synapses challenging. We will develop a new mouse model in which channelrhodopsin is selectively expressed in mossy cells and subsequently photostimulate inputs to granule cells or hilar interneurons independent of either perforant path or CA3 collaterals. Pre- and postsynaptic function, mechanisms of short- and long-term synaptic plasticity, and the role of kainate receptors at these synapses will be determined for the first time. These studies will elucidate the physiological role played by kainate receptors in hilar circuits and lay the framework for understanding their pathological role in network hyperexcitability in seizure states.

描述（由申请人提供）：门区苔藓细胞是重要的，但相对较少研究皮层输入到海马体的整合。信号