Parvalbumin interneurons regulate nucleus accumbens synapses and behavior

小清蛋白中间神经元调节伏隔核突触和行为

基本信息

  • 批准号:
    10675558
  • 负责人:
  • 金额:
    $ 47.8万
  • 依托单位:
  • 依托单位国家:
    美国
  • 项目类别:
  • 财政年份:
    2016
  • 资助国家:
    美国
  • 起止时间:
    2016-09-01 至 2026-05-31
  • 项目状态:
    未结题

项目摘要

PROJECT SUMMARY Substance use disorders (SUDs) remain a medical and societal burden with a relative paucity of prevention and treatment options. The nucleus accumbens (NAc) is an essential hub integrating cognitive, contextual, sensory and affective information into behavioral outcomes. Changes in excitatory (glutamatergic) synaptic function in the NAc is a leading molecular mechanism by which illicit drug exposure leads to the behavioral manifestations represented by SUDs. However, a gap in the input specificity, temporal dynamic, mechanism(s) and consequences of plasticity and drug-induced plasticity onto parvalbumin expressing fast spiking interneurons (PV-FSIs) remains. The long-term goal is to understand the mechanisms by which NAc circuits mediate reinforced behaviors. The overall objective of this application is: (1) to define input-specific plasticity mechanisms controlling excitatory synaptic strength onto PV-FSIs, (2) to elucidate mechanistic contributions of these synapses to reinforcement behavior, and (3) to determine contribution of NAc PV-FSI AMPA receptors to cocaine-evoked plasticity of MSN excitatory synapses. The central hypothesis is that functionally-distinct corticolimbic and thalamic synapses onto PV-FSIs in the NAc support cocaine-evoked adaptations in reinforcement behavior and circuit function. Aim 1 is designed to determine mechanisms of stimulus and cocaine-evoked synaptic plasticity of specific excitatory inputs onto NAc PV-FSIs. Aim 2 will determine the role of glutamatergic signaling onto NAc PV-FSIs in modulating reinforcement behavior in an input specific manner. And, Aim 3 will elucidate the contribution of NAc PV-FSI AMPA receptors to cocaine-induced plasticity of MSNs. The rationale for the proposed studies is that they will provide a detailed understanding of the functional organization of NAc PV-FSI microcircuitry, revealing synaptic mechanisms by which PV-FSIs adapt to stimuli and support reinforcement behavior as well as influence cocaine-evoked reorganization of output circuits. To accomplish these aims a combination of whole-cell patch clamp electrophysiology, Drugs Acutely Restricted by Tethering (DART) pharmacology, optogenetics, reinforcement behavior and transgenic mice will be used. The proposed research is innovative because it represents a new and substantive departure from the status quo by shifting focus to the modulation of PV-FSI feedforward inhibition as a master regulator of NAc function and thus reward-related behavior. Completion of the work in this proposal will: (1) establish plasticity mechanisms at specific excitatory inputs onto PV-FSIs. (2) Establish a causal relationship between NAc PV-FSI AMPA receptors and reinforcement behavior and (3) demonstrate that NAc PV-FSI AMPA receptors are necessary for cocaine- evoked plasticity of MSN excitatory synapses. Completion of this work is expected to have a positive translational impact by examining an understudied but integral component of the reward system and will provide a launching point for the development of novel strategies to prevent and treat Substance Use Disorders.
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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Brad Alan Grueter其他文献

Brad Alan Grueter的其他文献

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{{ truncateString('Brad Alan Grueter', 18)}}的其他基金

Photoperiodic Programming of Monoamine Brain Circuits
单胺脑回路的光周期编程
  • 批准号:
    10735447
  • 财政年份:
    2023
  • 资助金额:
    $ 47.8万
  • 项目类别:
Parvalbumin interneurons regulate nucleus accumbens synapses and behavior
小白蛋白中间神经元调节伏隔核突触和行为
  • 批准号:
    10487428
  • 财政年份:
    2016
  • 资助金额:
    $ 47.8万
  • 项目类别:
Parvalbumin interneurons regulate nucleus accumbens synapses and behavior
小清蛋白中间神经元调节伏隔核突触和行为
  • 批准号:
    10298824
  • 财政年份:
    2016
  • 资助金额:
    $ 47.8万
  • 项目类别:
Parvalbumin interneurons regulate nucleus accumbens synapses and behavior
小白蛋白中间神经元调节伏隔核突触和行为
  • 批准号:
    10161984
  • 财政年份:
    2016
  • 资助金额:
    $ 47.8万
  • 项目类别:
Parvalbumin interneurons regulate nucleus accumbens synapses and behavior
小清蛋白中间神经元调节伏隔核突触和行为
  • 批准号:
    9923260
  • 财政年份:
    2016
  • 资助金额:
    $ 47.8万
  • 项目类别:
Parvalbumin interneurons regulate nucleus accumbens synapses and behavior
小白蛋白中间神经元调节伏隔核突触和行为
  • 批准号:
    9698739
  • 财政年份:
    2016
  • 资助金额:
    $ 47.8万
  • 项目类别:
Parvalbumin interneurons regulate nucleus accumbens synapses and behavior
小清蛋白中间神经元调节伏隔核突触和行为
  • 批准号:
    9174760
  • 财政年份:
    2016
  • 资助金额:
    $ 47.8万
  • 项目类别:
Synaptic Mechanisms of Addiction-Related Behaviors in the Nucleus Accumbens
伏核成瘾相关行为的突触机制
  • 批准号:
    8585390
  • 财政年份:
    2013
  • 资助金额:
    $ 47.8万
  • 项目类别:
Synaptic Mechanisms of Addiction-Related Behaviors in the Nucleus Accumbens
伏核成瘾相关行为的突触机制
  • 批准号:
    8637959
  • 财政年份:
    2013
  • 资助金额:
    $ 47.8万
  • 项目类别:
Synaptic Mechanisms of Addiction-Related Behaviors in the Nucleus Accumbens
伏核成瘾相关行为的突触机制
  • 批准号:
    8825475
  • 财政年份:
    2013
  • 资助金额:
    $ 47.8万
  • 项目类别:

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  • 批准号:
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  • 财政年份:
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  • 财政年份:
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