Role of astrocytes in dopamine signaling and psychostimulant effects

星形胶质细胞在多巴胺信号传导和精神兴奋作用中的作用

基本信息

  • 批准号:
    9797456
  • 负责人:
  • 金额:
    $ 33.97万
  • 依托单位:
  • 依托单位国家:
    美国
  • 项目类别:
  • 财政年份:
    2019
  • 资助国家:
    美国
  • 起止时间:
    2019-08-01 至 2024-05-31
  • 项目状态:
    已结题

项目摘要

Dopamine (DA) signaling is involved in a plethora of brain functions, including motor control, learning and memory, and reward. It is affected by the psychostimulants amphetamine and cocaine, which are thought to act by increasing the extracellular DA levels. In contrast to the extensive studies in neurons, the involvement of astrocytes in DA signaling and psychostimulant actions remain largely unexplored. Astrocytes play supportive roles in brain function, and they can also influence neuronal and synaptic activity through the bidirectional communication with neurons in tripartite synapses. Astrocytes respond with calcium elevations to several neurotransmitters (such as glutamate, acetylcholine, or endocannabinoids), and release gliotransmitters that modulate synaptic transmission. However, whether astrocytes respond to DA and consequently regulate neurotransmission remain largely unknown. The present proposal aims to define the involvement of astrocytes in DA signaling in the nucleus accumbens (NAc), a limbic area implicated in reward and addiction, and to identify the astrocyte contribution to the actions of the psychostimulant amphetamine. We hypothesize that astrocytes participate in the cellular mechanisms and functional consequences of DA signaling in the NAc and, as a consequence, they contribute to the synaptic effects of amphetamine. Our preliminary results indicate that DA activates astrocytes in the NAc, which stimulates the release of the gliotransmitter adenosine that regulates excitatory synaptic transmission. The present proposal will: 1) define the cellular mechanisms underlying DA control of the astrocyte activity in the NAc; 2) determine the consequences of DA-mediated astrocyte activity on synaptic transmission; 3) determine the actions of amphetamine on both astrocytic activity and astrocyte-mediated synaptic regulation. We will use state-of-the-art techniques, including pharmacogenetics (“designer receptors exclusively activated by designer drugs”, DREADDs), optogenetics to selectively stimulate dopaminergic axons, simultaneous two-photon Ca2+ imaging and electrophysiological recordings, and transgenic mice. The expected results will reveal astrocytes as cellular elements involved in DA signaling, thus contributing to the effects of amphetamine. They will define the astrocyte-neuron interactions in the NAc at the cellular level, paving the way for future studies recognizing astrocytes as elements involved in behaviors associated with reward as well as psychostimulant drugs. If astrocytes are involved in DA signaling, and astrocyte- neuron communication is affected by psychostimulants, this will reveal novel mechanisms that may serve as therapeutic targets in motivation disorders such as drug addiction.
多巴胺(DA)信号参与了大量的大脑功能,包括运动控制、学习和认知

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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Alfonso Araque其他文献

Alfonso Araque的其他文献

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{{ truncateString('Alfonso Araque', 18)}}的其他基金

Astrocyte activity in amygdala-related fear conditioned behaviors
杏仁核相关恐惧条件行为中的星形胶质细胞活性
  • 批准号:
    10400074
  • 财政年份:
    2020
  • 资助金额:
    $ 33.97万
  • 项目类别:
Astrocyte activity in amygdala-related fear conditioned behaviors
杏仁核相关恐惧条件行为中的星形胶质细胞活性
  • 批准号:
    10593940
  • 财政年份:
    2020
  • 资助金额:
    $ 33.97万
  • 项目类别:
Astrocyte activity in amygdala-related fear conditioned behaviors
杏仁核相关恐惧条件行为中的星形胶质细胞活性
  • 批准号:
    10176598
  • 财政年份:
    2020
  • 资助金额:
    $ 33.97万
  • 项目类别:
Role of astrocytes in dopamine signaling and psychostimulant effects
星形胶质细胞在多巴胺信号传导和精神兴奋作用中的作用
  • 批准号:
    10160869
  • 财政年份:
    2019
  • 资助金额:
    $ 33.97万
  • 项目类别:
Role of astrocytes in dopamine signaling and psychostimulant effects
星形胶质细胞在多巴胺信号传导和精神兴奋作用中的作用
  • 批准号:
    9977148
  • 财政年份:
    2019
  • 资助金额:
    $ 33.97万
  • 项目类别:
Role of astrocytes in dopamine signaling and psychostimulant effects
星形胶质细胞在多巴胺信号传导和精神兴奋作用中的作用
  • 批准号:
    10405093
  • 财政年份:
    2019
  • 资助金额:
    $ 33.97万
  • 项目类别:
Role of astrocytes in dopamine signaling and psychostimulant effects
星形胶质细胞在多巴胺信号传导和精神兴奋作用中的作用
  • 批准号:
    10629299
  • 财政年份:
    2019
  • 资助金额:
    $ 33.97万
  • 项目类别:
Tau-dependent cognitive deficits in alpha-synucleinopathies
α-突触核蛋白病中 Tau 依赖性认知缺陷
  • 批准号:
    10362640
  • 财政年份:
    2018
  • 资助金额:
    $ 33.97万
  • 项目类别:
Tau-dependent cognitive deficits in alpha-synucleinopathies
α-突触核蛋白病中 Tau 依赖性认知缺陷
  • 批准号:
    10112975
  • 财政年份:
    2018
  • 资助金额:
    $ 33.97万
  • 项目类别:
Astrocyte-neuron interaction in behavior driven by striatal information processing
纹状体信息处理驱动的行为中星形胶质细胞-神经元的相互作用
  • 批准号:
    9153346
  • 财政年份:
    2016
  • 资助金额:
    $ 33.97万
  • 项目类别:

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