GABA Receptors and Hilar Neuron Survival in Epilepsy
癫痫中的 GABA 受体和肺门神经元存活
基本信息
- 批准号:8968872
- 负责人:
- 金额:$ 33.69万
- 依托单位:
- 依托单位国家:美国
- 项目类别:
- 财政年份:2012
- 资助国家:美国
- 起止时间:2012-02-01 至 2017-01-31
- 项目状态:已结题
- 来源:
- 关键词:Animal ModelAnimalsBiological PreservationBrainCell surfaceCellsCerebellumConfocal MicroscopyD CellsElectron MicroscopyElectronsElectrophysiology (science)EpilepsyExhibitsGABA ReceptorGene ExpressionGlutamatesGoalsHilarHippocampal FormationHippocampus (Brain)HumanIn VitroInterneuronsIschemiaLabelLeadLightLocationMapsMediatingMediator of activation proteinMethodsMicroscopicModelingMusNeuronsPatternPilocarpinePlayPredispositionProcessProteinsPublic HealthReagentResearchRoleSeizuresSiteSomatostatinStatus EpilepticusSubgroupSuggestionTemporal Lobe EpilepsyTestingTraumatic Brain InjuryViral Genesadeno-associated viral vectorbasecell typedentate gyrusgranule cellin vivointerestneuron lossneuronal circuitryneuronal excitabilityneuroprotectionnew technologyoptogeneticsreceptorrecombinaseresponse
项目摘要
Project Summary
Loss of neurons in the hilus of the dentate gyrus is one of the most consistent morphological findings in
humans with temporal lobe epilepsy and related models of acquired epilepsy. Two major groups of hilar
neurons are frequently damaged, GABAergic somatostatin interneurons and glutamatergic mossy cells.
Despite years of interest in hilar neurons, important questions persist. Why are the neurons so vulnerable to
excitotoxic damage? How could they be protected? What are the functional effects of both loss and
preservation of subgroups of these neurons? A set of new technologies, reagents and mice will now allow
probing these questions in exciting new ways. The proposed studies will use mice with Cre-recombinase
expression in these neurons to selectively manipulate them through Cre-activated viral gene expression. A
combination of light and electron microscopic immunohistochemical methods will be used to evaluate the
changes, and functional correlates will be determined with electrophysiological methods. The broad goals are
to determine if increasing tonic GABAergic inhibition in these neurons could be neuroprotective and, in a
separate set of studies, to map the functional circuits that are activated following manipulation of either mossy
cells or somatostatin neurons in normal and seizure-prone animals in vivo. Specific Aim 1 will test the
hypothesis that both groups of hilar neurons lack substantial expression of the ¿ subunit of the GABAA receptor
(GABAAR) and have low levels of tonic inhibition. Specific Aim 2 will test the hypothesis that expressing an
exogenous GABAAR subunit, which is normally involved in tonic inhibition in the cerebellum, will lead to the
formation of functional GABAA receptors and increase tonic inhibition in both groups of hilar neurons. Specific
Aim 3 will test the hypothesis that increasing tonic inhibition in hilar neurons will protect them from damage
following status epilepticus. Specific Aim 4 will examine the functional circuitry of hilar neurons in vivo by using
optogenetic methods to manipulate the neurons selectively and then identifying the activated neurons by Fos
labeling. The patterns of activation in normal and seizure-prone animals will be compared to test the
hypotheses that stimulating remaining mossy cells or silencing remaining somatostatin interneurons in vivo will
lead to increased granule cell activation in the epileptic mice. By allowing selective manipulation of hilar
neurons in the intact brain, these studies will provide unique views of their function within normal and altered
neuronal circuits.
项目总结
项目成果
期刊论文数量(0)
专著数量(0)
科研奖励数量(0)
会议论文数量(0)
专利数量(0)
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CAROLYN R HOUSER其他文献
CAROLYN R HOUSER的其他文献
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{{ truncateString('CAROLYN R HOUSER', 18)}}的其他基金
GABA System Alterations and Fragile X Syndrome
GABA 系统改变和脆性 X 综合征
- 批准号:
8234488 - 财政年份:2012
- 资助金额:
$ 33.69万 - 项目类别:
2012 Mechanisms of Epilepsy and Neuronal Synchronization Gordon Research Conferen
2012 癫痫机制和神经元同步戈登研究会议
- 批准号:
8306407 - 财政年份:2012
- 资助金额:
$ 33.69万 - 项目类别:
GABA Receptors and Hilar Neuron Survival in Epilepsy
癫痫中的 GABA 受体和肺门神经元存活
- 批准号:
8413046 - 财政年份:2012
- 资助金额:
$ 33.69万 - 项目类别:
GABA System Alterations and Fragile X Syndrome
GABA 系统改变和脆性 X 综合征
- 批准号:
8606484 - 财政年份:2012
- 资助金额:
$ 33.69万 - 项目类别:
GABA Receptors and Hilar Neuron Survival in Epilepsy
癫痫中的 GABA 受体和肺门神经元存活
- 批准号:
8585940 - 财政年份:2012
- 资助金额:
$ 33.69万 - 项目类别:
GABA System Alterations and Fragile X Syndrome
GABA 系统改变和脆性 X 综合征
- 批准号:
8426129 - 财政年份:2012
- 资助金额:
$ 33.69万 - 项目类别:
GABA Receptors and Hilar Neuron Survival in Epilepsy
癫痫中的 GABA 受体和肺门神经元存活
- 批准号:
8293815 - 财政年份:2012
- 资助金额:
$ 33.69万 - 项目类别:
GABA System Alterations and Fragile X Syndrome
GABA 系统改变和脆性 X 综合征
- 批准号:
9008056 - 财政年份:2012
- 资助金额:
$ 33.69万 - 项目类别:
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