Cortico-limbic Circuits for Learning and Memory

学习和记忆的皮质边缘回路

基本信息

  • 批准号:
    RGPIN-2016-04364
  • 负责人:
  • 金额:
    $ 2.26万
  • 依托单位:
  • 依托单位国家:
    加拿大
  • 项目类别:
    Discovery Grants Program - Individual
  • 财政年份:
    2016
  • 资助国家:
    加拿大
  • 起止时间:
    2016-01-01 至 2017-12-31
  • 项目状态:
    已结题

项目摘要

This renewal extends a basic research project focused on neural mechanisms of synaptic plasticity required for learning and memory. We have made significant progress in understanding the role of synaptic Long-Term Depression (LTD) in the learning of fear conditioning and other aspects of memory including stress-induced disruption of spatial memories. A better understanding of the role of LTD in cognition will enhance our understanding of the biological bases of learning and memory. Success is due to the development of a small artificial peptide (‘3Y-interference peptide’-patent-pending) that disrupts the regulated endocytosis of the AMPA class of ionotropic glutamate receptors the critical final step in the induction of LTD. This allows for the manipulation of LTD at different stages of the learning/memory cascade. Our research strategy also requires sophisticated and reliable behavioral tests to assess specific aspects of learning and memory in rodents. The proposed experiments will utilize : 1) Attentional set-shifting requiring a switch in choice of which lever to press for food reward, based on location of the lever or position of a discriminative light cue; 2) Latent Inhibition (LI) of 2-way active avoidance responding in which repeated pre-exposure to a salient discriminative stimulus causes significant retardation in the acquisition of avoidance responses; 3) Discriminative stimulus learning whereby brief presentation of a specific sensory stimulus such as a tone or light predicts time-limited access to food reward. Related experiments will identify specific brain regions where disruption of LTD causes selective disruption of one or more of the learned behaviors. Direct evidence that the ‘interference peptide’ disrupts LTD in specific regions of the brain, will be provided by blocking LTD within specific brain regions by i.v administration of the ‘interference peptide’. Previous NSERC-funded research on the functional nature of synaptic plasticity revealed that direct electrical stimulation of glutamatergic afferents to the hippocampus can serve as a discriminative stimulus in the acquisition of a new response for food reward which in turn was enhanced significantly by induction of long-term potentiation (LTP). Our highly selective technique for blocking LTD in brain, coupled with our brain-stimulation signal detection procedure will provide a unique opportunity to resolve a fundamental issue in the study of synaptic plasticity and memory the functional effects of ‘ LTD-induced depotentiation” of LTP. In summary, the present proposal builds on our recent success in linking LTD to processes responsible for response flexibility and extinction of previously acquired memory. Collectively this research has significant theoretical importance and should provide new insights into the relationship between synaptic plasticity and information processing in brain.
这一更新扩展了一个基础研究项目,该项目专注于学习和记忆所需的突触可塑性的神经机制。我们在理解突触长期抑郁(LTD)在学习恐惧、条件反射和其他记忆方面的作用方面取得了重大进展,包括应激诱导的空间记忆中断。更好地理解LTD在认知中的作用将增强我们对学习和记忆的生物学基础的理解。 成功的原因是开发了一种小的人造多肽(正在申请专利的3Y干扰多肽),它扰乱了AMPA类离子谷氨酸受体的调节内吞作用,这是诱导LTD的关键最后一步。这允许在学习/记忆级联的不同阶段操纵LTD。我们的研究策略还需要复杂可靠的行为测试来评估啮齿动物学习和记忆的特定方面。建议的实验将利用:1)注意定势转换,需要根据控制杆的位置或辨别性光提示的位置,切换选择按下哪个控制杆来获得食物奖励;2)双向主动回避反应的潜在抑制(LI),在这种反应中,重复预先暴露于显著的歧视性刺激会导致回避反应的获得显著延迟;3)辨别性刺激学习,通过短暂呈现特定的感觉刺激,如音调或光,预测获得食物奖励的时间限制。相关实验将识别特定的大脑区域,在这些区域,LTD的干扰会导致一个或多个习得行为的选择性中断。通过静脉注射‘干扰肽’,阻断特定脑区的LTD将提供直接证据,证明‘干扰肽’在大脑的特定区域干扰LTD。 以前由NSERC资助的关于突触可塑性的功能性质的研究表明,对海马区谷氨酸能传入的直接电刺激可以在获得对食物奖励的新反应时作为一种区别性刺激,而这种反应又通过诱导长时程增强(LTP)而显着增强。我们在脑内高度选择性地阻断LTD的技术,再加上我们的脑刺激信号检测程序,将提供一个独特的机会来解决突触可塑性和记忆LTP‘LTD诱导的去增强’的功能效应‘研究中的一个基本问题。 总之,本提案建立在我们最近成功地将LTD与负责应对灵活性和消除先前获得的记忆的进程联系起来的基础上。总体而言,这项研究具有重要的理论意义,并将为突触可塑性与大脑信息处理之间的关系提供新的见解。

项目成果

期刊论文数量(0)
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Phillips, Anthony其他文献

Connexin dynamics in the privileged wound healing of the buccal mucosa
  • DOI:
    10.1111/wrr.12054
  • 发表时间:
    2013-07-01
  • 期刊:
  • 影响因子:
    2.9
  • 作者:
    Davis, Nicola G.;Phillips, Anthony;Becker, David L.
  • 通讯作者:
    Becker, David L.
Tracking Antioxidant Status in Spinal Cord Injured Rodents: A Voltammetric Method Suited for Clinical Translation
  • DOI:
    10.1016/j.wneu.2022.01.099
  • 发表时间:
    2022-04-29
  • 期刊:
  • 影响因子:
    2
  • 作者:
    Bringans, Cameron;Hammond, Callum;Phillips, Anthony
  • 通讯作者:
    Phillips, Anthony

Phillips, Anthony的其他文献

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{{ truncateString('Phillips, Anthony', 18)}}的其他基金

Cortico-limbic Circuits for Learning and Memory
学习和记忆的皮质边缘回路
  • 批准号:
    RGPIN-2016-04364
  • 财政年份:
    2021
  • 资助金额:
    $ 2.26万
  • 项目类别:
    Discovery Grants Program - Individual
Cortico-limbic Circuits for Learning and Memory
学习和记忆的皮质边缘回路
  • 批准号:
    RGPIN-2016-04364
  • 财政年份:
    2020
  • 资助金额:
    $ 2.26万
  • 项目类别:
    Discovery Grants Program - Individual
Cortico-limbic Circuits for Learning and Memory
学习和记忆的皮质边缘回路
  • 批准号:
    RGPIN-2016-04364
  • 财政年份:
    2019
  • 资助金额:
    $ 2.26万
  • 项目类别:
    Discovery Grants Program - Individual
Cortico-limbic Circuits for Learning and Memory
学习和记忆的皮质边缘回路
  • 批准号:
    RGPIN-2016-04364
  • 财政年份:
    2018
  • 资助金额:
    $ 2.26万
  • 项目类别:
    Discovery Grants Program - Individual
Cortico-limbic Circuits for Learning and Memory
学习和记忆的皮质边缘回路
  • 批准号:
    RGPIN-2016-04364
  • 财政年份:
    2017
  • 资助金额:
    $ 2.26万
  • 项目类别:
    Discovery Grants Program - Individual
Cortico-limbic circuits for learning and memory
用于学习和记忆的皮质边缘回路
  • 批准号:
    7808-2011
  • 财政年份:
    2015
  • 资助金额:
    $ 2.26万
  • 项目类别:
    Discovery Grants Program - Individual
Cortico-limbic circuits for learning and memory
用于学习和记忆的皮质边缘回路
  • 批准号:
    7808-2011
  • 财政年份:
    2014
  • 资助金额:
    $ 2.26万
  • 项目类别:
    Discovery Grants Program - Individual
Cortico-limbic circuits for learning and memory
用于学习和记忆的皮质边缘回路
  • 批准号:
    7808-2011
  • 财政年份:
    2013
  • 资助金额:
    $ 2.26万
  • 项目类别:
    Discovery Grants Program - Individual
Cortico-limbic circuits for learning and memory
用于学习和记忆的皮质边缘回路
  • 批准号:
    7808-2011
  • 财政年份:
    2012
  • 资助金额:
    $ 2.26万
  • 项目类别:
    Discovery Grants Program - Individual
Cortico-limbic circuits for learning and memory
用于学习和记忆的皮质边缘回路
  • 批准号:
    7808-2011
  • 财政年份:
    2011
  • 资助金额:
    $ 2.26万
  • 项目类别:
    Discovery Grants Program - Individual

相似海外基金

Cortico-limbic Circuits for Learning and Memory
学习和记忆的皮质边缘回路
  • 批准号:
    RGPIN-2016-04364
  • 财政年份:
    2021
  • 资助金额:
    $ 2.26万
  • 项目类别:
    Discovery Grants Program - Individual
Delineating cortico-limbic-striatal circuits in reward and punishment: segregation and integration
描绘奖励和惩罚中的皮质-边缘-纹状体回路:分离和整合
  • 批准号:
    RGPIN-2016-05638
  • 财政年份:
    2021
  • 资助金额:
    $ 2.26万
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    Discovery Grants Program - Individual
Delineating cortico-limbic-striatal circuits in reward and punishment: segregation and integration
描绘奖励和惩罚中的皮质-边缘-纹状体回路:分离和整合
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    RGPIN-2016-05638
  • 财政年份:
    2020
  • 资助金额:
    $ 2.26万
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Cortico-limbic Circuits for Learning and Memory
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  • 批准号:
    RGPIN-2016-04364
  • 财政年份:
    2020
  • 资助金额:
    $ 2.26万
  • 项目类别:
    Discovery Grants Program - Individual
Cortico-limbic Circuits for Learning and Memory
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  • 批准号:
    RGPIN-2016-04364
  • 财政年份:
    2019
  • 资助金额:
    $ 2.26万
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描绘奖励和惩罚中的皮质-边缘-纹状体回路:分离和整合
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  • 财政年份:
    2019
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    $ 2.26万
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Cortico-limbic Circuits for Learning and Memory
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  • 资助金额:
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描绘皮质-边缘-纹状体回路对食欲和厌恶动机行为的离散和上下文控制
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描绘奖励和惩罚中的皮质-边缘-纹状体回路:分离和整合
  • 批准号:
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描绘皮质-边缘-纹状体回路对食欲和厌恶动机行为的离散和上下文控制
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