Probing GABAa receptor function and plasticity with light
用光探测 GABAa 受体功能和可塑性
基本信息
- 批准号:9286699
- 负责人:
- 金额:$ 48.84万
- 依托单位:
- 依托单位国家:美国
- 项目类别:
- 财政年份:2017
- 资助国家:美国
- 起止时间:2017-04-15 至 2021-01-31
- 项目状态:已结题
- 来源:
- 关键词:AlcoholismAlzheimer&aposs DiseaseAnxietyBipolar DisorderBrainBrain DiseasesBrain regionCell Culture TechniquesCell membraneChemicalsDevelopmentDiseaseDistalEnsureEpilepsyGABA ReceptorGeneticGlutamate ReceptorGlutamatesGoalsHippocampus (Brain)Hot SpotIndividualInhibitory SynapseInterneuronsIntrabodyKnock-in MouseKnowledgeLabelLateralLearningLearning DisordersLightLong-Term DepressionLong-Term PotentiationLongevityMapsMeasuresMediatingMembraneMemoryMemory DisordersMental DepressionMusN-Methyl-D-Aspartate ReceptorsNeuronsNeurotransmittersPhotosensitivityPhotosensitizationPhysiologicalPlayProcessProtein IsoformsReceptor SignalingRoleScaffolding ProteinSchizophreniaSiteSleeplessnessSpecific qualifier valueSpecificityStrokeSynapsesSynaptic TransmissionSynaptic plasticityTimeWorkbrain cellcell typechronic paingamma-Aminobutyric Acidmutantnervous system disordernovelreceptorreceptor functionresponsescaffoldsynaptic functiontooltraffickingtreatment strategytwo-photon
项目摘要
GABA and glutamate are the main inhibitory and excitatory neurotransmitters in the brain.
Activity-dependent redistribution of glutamate receptors contributes to excitatory long-term
synaptic plasticity, learning and memory. A similar redistribution of GABAA receptors
(GABAARs) has been shown to occur in neuronal culture, but the functional significance of this
process in intact brain circuits remains unclear. Our goal is to better understand the role that
GABAA receptors play in synaptic plasticity in the hippocampus, a brain region crucial for
learning and memory. We have developed photoswitch chemicals that allow light to reversibly
block GABAA receptors with high spatial and temporal precision and absolute specificity for a
specified mutant α-subunit. Here we focus on receptors containing either the broadly-
expressed α1-subunit, or the hippocampus-enriched α5-subunit. To enable photo-control of
endogenous receptors, we have developed knock-in mice with photoswitch-ready version of α1
or α5 replacing their wild-type counterparts. Using these mice and novel intrabody probes that
light-up or disrupt GABAARs scaffolds, we will evaluate where α1- and α5-GABAARs are in
neurons, how they contribute to synaptic function, and what role they play in synaptic
plasticity. Aim 1 is to map the distribution of the two GABAA types in hippocampal neurons.
This includes determining whether they are expressed in proximal to distal dendritic gradients,
determining whether they are aggregated at synapses or dispersed extrasynapatically, and
determining their individual contributions to inhibitory synaptic transmission from different
identified inhibitory interneurons. Aim 2 is to investigate how neuronal activity alters the
distribution of GABAARs. This includes using the photoswitch as a stable tag to evaluate
whether activity alters the lifespan and lateral mobility of the receptors on the plasma
membrane. Aim 3 is to investigate how GABAARs alter excitatory long-term synaptic
plasticity. This includes investigating the impact of the GABAARs on induction of long-term
potentiation and depression and NMDA receptor signaling. The knowledge gained from this
work will fill a gaping hole in our understanding of brain function and may reveal new
treatment strategies for memory disorders and other neurological diseases.
!
GABA和谷氨酸是大脑中主要的抑制性和兴奋性神经递质。
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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RICHARD H KRAMER其他文献
RICHARD H KRAMER的其他文献
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{{ truncateString('RICHARD H KRAMER', 18)}}的其他基金
An electro-mechanical mechanism of spike propagation in myelinated axons
有髓轴突中尖峰传播的机电机制
- 批准号:
10194107 - 财政年份:2021
- 资助金额:
$ 48.84万 - 项目类别:
Targeting the retinoic acid signaling pathway for mitigating visual impairmen in retinal degenerative disorders
靶向视黄酸信号通路以减轻视网膜退行性疾病中的视力障碍
- 批准号:
10298375 - 财政年份:2015
- 资助金额:
$ 48.84万 - 项目类别:
Targeting the retinoic acid signaling pathway for mitigating visual impairmen in retinal degenerative disorders
靶向视黄酸信号通路以减轻视网膜退行性疾病中的视力障碍
- 批准号:
10475753 - 财政年份:2015
- 资助金额:
$ 48.84万 - 项目类别:
Targeting the retinoic acid signaling pathway for mitigating visual impairmen in retinal degenerative disorders
靶向视黄酸信号通路以减轻视网膜退行性疾病中的视力障碍
- 批准号:
10844853 - 财政年份:2015
- 资助金额:
$ 48.84万 - 项目类别:
Understanding How Photoswitches Restore Visual Function in Blind Mice
了解光电开关如何恢复失明小鼠的视觉功能
- 批准号:
9330653 - 财政年份:2015
- 资助金额:
$ 48.84万 - 项目类别:
Understanding how photoswitches restore visual function in blindness
了解光电开关如何恢复失明者的视觉功能
- 批准号:
10212754 - 财政年份:2015
- 资助金额:
$ 48.84万 - 项目类别:
Targeting the retinoic acid signaling pathway for mitigating visual impairmen in retinal degenerative disorders
靶向视黄酸信号通路以减轻视网膜退行性疾病中的视力障碍
- 批准号:
10684166 - 财政年份:2015
- 资助金额:
$ 48.84万 - 项目类别:
A universal photoswitch system for optical control of neuronal receptors
用于神经元受体光学控制的通用光电开关系统
- 批准号:
7726422 - 财政年份:2009
- 资助金额:
$ 48.84万 - 项目类别:
A universal photoswitch system for optical control of neuronal receptors
用于神经元受体光学控制的通用光电开关系统
- 批准号:
8255457 - 财政年份:2009
- 资助金额:
$ 48.84万 - 项目类别:
A universal photoswitch system for optical control of neuronal receptors
用于神经元受体光学控制的通用光电开关系统
- 批准号:
7898562 - 财政年份:2009
- 资助金额:
$ 48.84万 - 项目类别:














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