Cortical GABAergic Circuits in Alzheimer's Disease
阿尔茨海默病中的皮质 GABA 能回路
基本信息
- 批准号:9293204
- 负责人:
- 金额:$ 20.91万
- 依托单位:
- 依托单位国家:美国
- 项目类别:
- 财政年份:
- 资助国家:美国
- 起止时间:至
- 项目状态:未结题
- 来源:
- 关键词:AcetylcholineAlzheimer&aposs DiseaseAlzheimer&aposs disease modelAmyloidAmyloid beta-ProteinAttentionAttentional deficitAutopsyBehaviorBehavioralBiological MarkersBrain DiseasesCholinesterase InhibitorsCognitiveDefectDepositionElectrophysiology (science)ExhibitsFaceFoundationsFunctional disorderFutureGoalsHippocampus (Brain)HumanHyperactive behaviorImmunohistochemistryImpairmentInterneuronsInterventionKnowledgeLeadLinkMeasuresMediatingMicroscopyMolecularMorphologyMusNeocortexNerve DegenerationNeurobehavioral ManifestationsNeuronsNicotinic ReceptorsOpticsOutcomePathologyPatientsPatternPerformancePhysiologyPlayPopulationPositioning AttributePrefrontal CortexPropertyQuality of lifeReaction TimeResearchResearch PersonnelRoleSample SizeSeizuresSignal TransductionSynapsesTestingTissuesViralWorkamyloid imagingbeta amyloid pathologycell typecholinergicdata managementdonepezilexcitatory neuronexperimental studyfrontal lobefunctional disabilitygamma-Aminobutyric Acidhippocampal pyramidal neuronhuman subjectin vivoinformation processinginhibitory neuronknock-downmouse modelneuropathologyneuroregulationneurotransmissionnoveloptogeneticsreceptor expressionreconstructionrelating to nervous systemsmall hairpin RNAspatiotemporalstatisticstheoriestooltwo-photon
项目摘要
PROJECT SUMMARY
Attentional deficits diminish the quality of life for Alzheimer's disease (AD) patients, however the neural
basis for this early impairment is not understood. In mouse models of AD, excitatory neurons are hyperactive
near amyloid deposits, which could contribute to defects in information processing underlying behavioral
dysfunctions. We hypothesize that hypofunction of cortical GABAergic circuits near amyloid deposits is
associated with the aberrant network activity and attentional deficits. To test this hypothesis, we will measure
the electrophysiological properties of the major subtypes of GABAergic neurons in an AD mouse model. We
will also characterize the dendritic morphologies of the inhibitory interneurons in an AD mouse model and in
post-mortem cortical tissue from AD patients. To test the prediction that cholinergic signaling in GABAergic
interneurons is compromised, we will measure the ability of acetylcholine to modulate cortical network activity.
We will also investigate whether knocking down nicotinic acetylcholine receptors in specific subtypes of
GABAergic interneurons can recapitulate the neuropathology. Finally, we will investigate the behavioral
relevance by determining whether activating specific GABAergic neuronal populations in the neocortex can
alleviate attentional deficits in an AD mouse model. These experiments leverage a combination of optical,
electrophysiological, molecular, and behavioral approaches to tease apart the circuit level neuropathology in
an AD mouse model. The results will position GABAergic neurotransmission as a point of integration for the
synaptic Abeta and cholinergic theories of AD. A positive outcome will also provide evidence for targeting
specific cell types for treating attentional deficits in AD.
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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CHUN-HAY ALEX KWAN其他文献
CHUN-HAY ALEX KWAN的其他文献
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{{ truncateString('CHUN-HAY ALEX KWAN', 18)}}的其他基金
Cellular basis of psilocybin actions in frontal cortex
额叶皮层裸盖菇素作用的细胞基础
- 批准号:
10516272 - 财政年份:2022
- 资助金额:
$ 20.91万 - 项目类别:
A Dendritic Substrate for Fast-Acting Antidepressant Action
具有快速抗抑郁作用的树突状基质
- 批准号:
10755878 - 财政年份:2022
- 资助金额:
$ 20.91万 - 项目类别:
Cellular basis of psilocybin actions in frontal cortex
额叶皮层裸盖菇素作用的细胞基础
- 批准号:
10686230 - 财政年份:2022
- 资助金额:
$ 20.91万 - 项目类别:
A Dendritic Substrate for Fast-Acting Antidepressant Action
具有快速抗抑郁作用的树突状基质
- 批准号:
10623145 - 财政年份:2022
- 资助金额:
$ 20.91万 - 项目类别:
A Dendritic Substrate for Fast-Acting Antidepressant Action
具有快速抗抑郁作用的树突状基质
- 批准号:
10386910 - 财政年份:2020
- 资助金额:
$ 20.91万 - 项目类别:
A Dendritic Substrate for Fast-Acting Antidepressant Action
具有快速抗抑郁作用的树突状基质
- 批准号:
10188646 - 财政年份:2020
- 资助金额:
$ 20.91万 - 项目类别:
Frontal cholinergic signals during value-based decision-making
基于价值的决策过程中的额叶胆碱能信号
- 批准号:
9789948 - 财政年份:2018
- 资助金额:
$ 20.91万 - 项目类别:
Structural plasticity basis of fast-acting antidepressant action
速效抗抑郁作用的结构可塑性基础
- 批准号:
9291526 - 财政年份:2016
- 资助金额:
$ 20.91万 - 项目类别:
Cortical GABAergic Circuits in Alzheimer's Disease
阿尔茨海默病中的皮质 GABA 能回路
- 批准号:
8849045 - 财政年份:
- 资助金额:
$ 20.91万 - 项目类别:














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