Dopamine modulation of network activity in the prefrontal cortex.

多巴胺调节前额皮质网络活动。

基本信息

  • 批准号:
    7256122
  • 负责人:
  • 金额:
    $ 18.81万
  • 依托单位:
  • 依托单位国家:
    美国
  • 项目类别:
  • 财政年份:
    2007
  • 资助国家:
    美国
  • 起止时间:
    2007-03-05 至 2009-02-28
  • 项目状态:
    已结题

项目摘要

DESCRIPTION (provided by applicant): Cortical activity in the intact brain is characterized by intermittent sustained membrane depolarizations called "up-states". The task-specific computations of a given cortical region are superimposed on top of this heightened activity. In the case of the prefrontal cortex (PFC), recurrent excitation of deep layer neurons is thought to underlie sustained activity during working memory. Dopamine (DA) modulates working memory, however, it has not been feasible to investigate its detailed biophysical effects in the awake animal. Instead, most of our knowledge about dopamine's effects on membrane excitability or synaptic transmission derives from recordings in "quiet" acute brain slice preparations. However, up-states and sustained activity are a network phenomenon and the asynchronous firing that occurs across neurons results from the interplay between intrinsic excitability and recurrent synaptic transmission. The present proposal investigates DA modulation of active cortex using an organotypic co-culture preparation of the PFC, hippocampus and ventral tegmental area (VTA). These cultures exhibit sustained activity (up-states) and possess key inputs required for working memory, namely the hippocampus and the DA input from the VTA. The present proposal tests two hypotheses generated from in vitro brain slice preparations and computational modeling studies. The first hypothesis posits that sustained activity during up-states can be modulated by DA in a dose-dependent manner. Experiments in Specific Aim 1 will use whole-cell current clamp recordings to test whether there is an "optimal" range of DA modulation in which action-potential firing and up-state duration are enhanced, while outside of this optimal range sustained activity will be reduced. Control experiments will assess the contribution of tonic vs. phasic release of DA from the VTA, and will test whether DA has network specific effects. The concentration of DA in the slice will be monitored simultaneously via fast-scan cyclic voltammetry. The second hypothesis states that DA acts on GABA and NMDA currents to modulate persistent activity during up-states. Combined voltage-clamp and calcium imaging experiments will be used to measure the modulation of GABA and NMDA currents by a high dose or low dose of DA, respectively. These studies will provide insights into the architecture of sustained activity and DA modulation of active PFC networks; information critical for our understanding of the normal and pathological conditions of the PFC.
描述(由申请人提供):完整脑中的皮质活动的特征在于称为“上升状态”的间歇性持续膜去极化。特定皮层区域的特定任务计算叠加在这种增强的活动之上。在前额叶皮层(PFC)的情况下,深层神经元的反复兴奋被认为是工作记忆期间持续活动的基础。多巴胺(DA)调节工作记忆,然而,它一直是不可行的,以探讨其详细的生物物理效应在清醒的动物。相反,我们关于多巴胺对膜兴奋性或突触传递的影响的大部分知识来自“安静”的急性脑切片准备的记录。然而,上升状态和持续的活动是一种网络现象,神经元之间发生的异步放电是由内在兴奋性和反复突触传递之间的相互作用引起的。本研究采用PFC、海马和腹侧被盖区(VTA)的器官型共培养制备来研究DA对活动皮层的调制。这些文化表现出持续的活动(高状态),并拥有工作记忆所需的关键输入,即海马体和来自VTA的DA输入。本提案测试两个假设产生的体外脑切片制备和计算建模研究。第一个假设假定,持续的活动在上升状态可以调制DA的剂量依赖性的方式。具体目标1中的实验将使用全细胞电流钳记录来测试是否存在DA调制的“最佳”范围,在该范围内动作电位放电和上升状态持续时间增强,而在该最佳范围之外持续活动将减少。对照实验将评估DA从腹侧被盖区的强直性与阶段性释放的贡献,并将测试DA是否具有网络特异性效应。通过快速扫描循环伏安法同时监测切片中DA的浓度。第二个假说指出,DA作用于GABA和NMDA电流,以调节持续的活动,在向上状态。结合电压钳和钙成像实验将被用来测量GABA和NMDA电流的调制高剂量或低剂量的DA,分别。这些研究将提供深入了解持续的活动和DA调制的主动PFC网络的架构;信息的正常和病理条件的PFC的理解至关重要。

项目成果

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SVEN KROENER其他文献

SVEN KROENER的其他文献

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{{ truncateString('SVEN KROENER', 18)}}的其他基金

Vagus nerve stimulation modulates synaptic plasticity in the rat prefrontal cortex during the extinction of drug-seeking
迷走神经刺激调节大鼠前额皮质在寻药消退过程中的突触可塑性
  • 批准号:
    10594495
  • 财政年份:
    2022
  • 资助金额:
    $ 18.81万
  • 项目类别:
Synaptic changes in the medial prefrontal cortex in the development of compulsive alcohol drinking
强迫性饮酒发展过程中内侧前额叶皮层的突触变化
  • 批准号:
    10732680
  • 财政年份:
    2022
  • 资助金额:
    $ 18.81万
  • 项目类别:
Synaptic changes in the medial prefrontal cortex in the development of compulsive alcohol drinking
强迫性饮酒发展过程中内侧前额叶皮层的突触变化
  • 批准号:
    10573176
  • 财政年份:
    2022
  • 资助金额:
    $ 18.81万
  • 项目类别:
Vagus nerve stimulation modulates synaptic plasticity in the rat prefrontal cortex during the extinction of drug-seeking
迷走神经刺激调节大鼠前额皮质在寻药消退过程中的突触可塑性
  • 批准号:
    10341341
  • 财政年份:
    2022
  • 资助金额:
    $ 18.81万
  • 项目类别:
Synaptic changes in the medial prefrontal cortex in the development of compulsive alcohol drinking
强迫性饮酒发展过程中内侧前额叶皮层的突触变化
  • 批准号:
    10367079
  • 财政年份:
    2022
  • 资助金额:
    $ 18.81万
  • 项目类别:
Effects of Chronic Alcohol Exposure on Synaptic Plasticity in the Prefrontal Cort
长期酒精暴露对前额皮质突触可塑性的影响
  • 批准号:
    7923710
  • 财政年份:
    2009
  • 资助金额:
    $ 18.81万
  • 项目类别:
Dopamine modulation of network activity in the prefrontal cortex.
多巴胺调节前额皮质网络活动。
  • 批准号:
    7369668
  • 财政年份:
    2007
  • 资助金额:
    $ 18.81万
  • 项目类别:

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