In vivo neurocircuitry of DBS response in rodents

啮齿类动物 DBS 反应的体内神经回路

基本信息

  • 批准号:
    8076854
  • 负责人:
  • 金额:
    $ 21.29万
  • 依托单位:
  • 依托单位国家:
    美国
  • 项目类别:
  • 财政年份:
    2010
  • 资助国家:
    美国
  • 起止时间:
    2010-06-01 至 2014-05-31
  • 项目状态:
    已结题

项目摘要

Imaging studies suggest that obsessive-compulsive disorder (OCD) may be due to overactivity within the lateral orbitofrontal cortex (LO); an area known to be important in stimulus valuation. Secondly, the vmPFC has been suggested to play a role based on its function in extinction. We propose that OCD is due to a dysfunction of hyperactivity within the LO, causing the patient to over-value a stimulus that is no longer behaviorally salient, and hypoactivity within the vmPFC, interfering with normal extinction of nonsalient stimuli. High-frequency stimulation (HFS) of the brain, is proposed to act therapeutically by restoring normal function to these circuits. This project uses in vivo recordings of LO and vmPFC activity and how these circuits respond to HFS of the NAc, which is the rodent analog of the stimulation site found to be effective in treating OCD in humans. Stimuli will be presented acutely, subchronically (90 min-8 hours), and chronically using implanted custom-designed stimulators (2 weeks) to evaluate the changes that occur during the course of stimulation. These changes will be evaluated in terms of rhythmic activity, neuronal firing, and synaptic plasticity changes that occur over these time intervals. A unique component to this proposal is that stimulation and most measurements will be performed in the awake animal to circumvent anesthesia issues. This study will be done along three specific aims: 1) Examine the effects of subchronic HFS stimulation of the NAc site on mPFC, LO and NAc spontaneous and evoked fields, along with c-fos to evaluate which neuron types are affected. 2) Examine chronic HFS effects on vmPFC, LO and NAc activity states and the time course of the changes. During the last day of stimulation, animals will be anesthetized and recordings of neurons identified by juxtacellular labeling and immunocytochemistry to assess the cellular nature of the changes observed. 3) Examine the effects of chronic HFS on mPFC-LO interactions to evaluate whether the changes observed in vmPFC are dependent on the LO, and vice-versa. We propose that HFS will decrease LO activity to decrease the emotional salience of the stimulus, while activating the mPFC to facilitate extinction; both of which may be required for a therapeutic response. Such information will provide essential data with respect to HFS effects at a systems level, as well as how network interactions can modulate regionally-selective alterations at the cellular level. Furthermore, this project will provide essential information to evaluate the imaging and clinical findings, the alterations in activity that will be tested in behavioral experiments, and the neuronal types activated for comparison with the in vitro cellular analyses. RELEVANCE (See instructions): This study will provide information regarding the modulation and interaction of cortical circuits proposed to have a role in OCD, as well as mechanisms by which rhythmic activity is modulated within these circuits. In addition, it will provide a cellular basis for the therapeutic effects of HFS used in the treatment of OCD, and help to refine the stimulation sites and parameters to most effectively induce the desired changes.
影像学研究表明,强迫症(OCD)可能是由于大脑内部的过度活动

项目成果

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专利数量(0)

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ANTHONY A GRACE其他文献

ANTHONY A GRACE的其他文献

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{{ truncateString('ANTHONY A GRACE', 18)}}的其他基金

Circuit-based Study of Depression/Anhedonia in Rats
大鼠抑郁/快感缺失的回路研究
  • 批准号:
    8694160
  • 财政年份:
    2014
  • 资助金额:
    $ 21.29万
  • 项目类别:
Circuit-based Study of Depression/Anhedonia in Rats
大鼠抑郁/快感缺失的回路研究
  • 批准号:
    9043194
  • 财政年份:
    2014
  • 资助金额:
    $ 21.29万
  • 项目类别:
Circumventing physiological consequences of drug abuse
规避药物滥用的生理后果
  • 批准号:
    8661742
  • 财政年份:
    2013
  • 资助金额:
    $ 21.29万
  • 项目类别:
Circumventing physiological consequences of drug abuse
规避药物滥用的生理后果
  • 批准号:
    8598969
  • 财政年份:
    2013
  • 资助金额:
    $ 21.29万
  • 项目类别:
INTEGRETIVE INFLUENCES OF THALAMIC/CORTICAL INPUTS--PREFRONTAL CORTICAL FUNCTION
丘脑/皮质输入的整体影响——前额皮质功能
  • 批准号:
    7553450
  • 财政年份:
    2007
  • 资助金额:
    $ 21.29万
  • 项目类别:
Stress-induced alterations in amygdala-LC interactions
压力引起的杏仁核-LC 相互作用的改变
  • 批准号:
    6919221
  • 财政年份:
    2003
  • 资助金额:
    $ 21.29万
  • 项目类别:
Stress-induced alterations in amygdala-LC interactions
压力引起的杏仁核-LC 相互作用的改变
  • 批准号:
    7217260
  • 财政年份:
    2003
  • 资助金额:
    $ 21.29万
  • 项目类别:
Stress-induced alterations in amygdala-LC interactions
压力引起的杏仁核-LC 相互作用的改变
  • 批准号:
    7618885
  • 财政年份:
    2003
  • 资助金额:
    $ 21.29万
  • 项目类别:
Stress-Induced Alterations in Amygdala-LC Interactions
压力引起的杏仁核-LC 相互作用的改变
  • 批准号:
    7645265
  • 财政年份:
    2003
  • 资助金额:
    $ 21.29万
  • 项目类别:
Stress-induced alterations in amygdala-LC interactions
压力引起的杏仁核-LC 相互作用的改变
  • 批准号:
    6721245
  • 财政年份:
    2003
  • 资助金额:
    $ 21.29万
  • 项目类别:
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