A Dendritic Substrate for Fast-Acting Antidepressant Action

具有快速抗抑郁作用的树突状基质

基本信息

  • 批准号:
    10188646
  • 负责人:
  • 金额:
    $ 53.87万
  • 依托单位:
  • 依托单位国家:
    美国
  • 项目类别:
  • 财政年份:
    2020
  • 资助国家:
    美国
  • 起止时间:
    2020-06-10 至 2025-04-30
  • 项目状态:
    未结题

项目摘要

PROJECT SUMMARY Our long-term goal is to understand how the structure and function of dendrites in the frontal cortex are affected by stress and antidepressants. Considerable evidence indicates that the action of fast-acting antidepressants such as ketamine relies on synaptic plasticity in the frontal cortex. An essential ingredient for plasticity is calcium influx in dendritic spines. However, to date, empirical data detailing how antidepressants may modulate calcium levels in dendritic spines in vivo are lacking. In preliminary studies, we used subcellular- resolution two-photon microscopy to visualize localized calcium transients in dendritic spines in the medial frontal cortex of the mouse in vivo. We found that the administration of the fast-acting antidepressant ketamine leads to an acute elevation of calcium signals in apical dendritic spines, due to a suppression of dendritic inhibition. On the basis of the preliminary results and prior research, we hypothesize that the enhanced synaptic calcium signal is a necessary step towards ketamine’s antidepressant action. In this project, we will determine the interactive effects of stress and ketamine on synaptic calcium signals (Aim 1). We will track morphology and calcium signals in the same dendritic spines to ask if the calcium elevations precede structural remodeling (Aim 2). We will determine if spines receiving inputs from specific long-range afferent regions are selectively targeted (Aim 3). Together, the results are expected to provide insights into the biological basis of ketamine’s action. As calcium is an essential checkpoint for synaptic plasticity in the frontal cortex, delineating its role in antidepressant action will accelerate the evaluation of candidate compounds and the development of more targeted treatments.
项目总结

项目成果

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会议论文数量(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:
    $ 53.87万
  • 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:
    $ 53.87万
  • 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:
    $ 53.87万
  • 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:
    $ 53.87万
  • 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:
    $ 53.87万
  • 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:
    $ 53.87万
  • 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:
    $ 53.87万
  • 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:
    9293204
  • 财政年份:
  • 资助金额:
    $ 53.87万
  • 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:
    $ 53.87万
  • 项目类别:

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