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:
  • 项目状态:
    未结题

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

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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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