The role of perineuronal nets in adult cognition

神经周围网在成人认知中的作用

基本信息

  • 批准号:
    RGPIN-2019-06102
  • 负责人:
  • 金额:
    $ 5.68万
  • 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:
    2021
  • 资助国家:
    加拿大
  • 起止时间:
    2021-01-01 至 2022-12-31
  • 项目状态:
    已结题

项目摘要

An emerging concept in neuroscience is that brain plasticity is dependent not only on neurons and glia, but also on structures present outside of these cells. The extracellular matrix-which comprises about 20% of the brain's volume (1) and contributes to neuronal and glial communication (2)-is a prime candidate for this role. Indeed, recent evidence from my lab suggests that one extracellular matrix component called a perineuronal net (PNN) may go beyond it's established role in neurodevelopment and contribute to fundamental learning and memory processes in the adult brain. The overarching goal of this research program is to develop a comprehensive understanding of mechanisms by which PNNs are involved in adult cognition. PNNs are a component of the extracellular matrix that are primarily found wrapped around inhibitory, parvalbumin positive cortical neurons. PNNs form during development, and are central in the closure of critical periods of heightened synaptic plasticity during development to lower levels during adulthood(3). Enzymatic degradation of chondroitin sulphate proteoglycans (CSPGs), major components of PNNs, can re-open the juvenile critical period for ocular dominance plasticity in adult rats (3) and can facilitate recovery from spinal cord injury and other forms of damage to the nervous system(4,5). Synaptic plasticity is also essential for learning and memory across the lifespan(6-8), however, almost no work has investigated whether PNNs contribute to fundamental learning and memory processes in the adult brain. Recent work from my lab has shown that depletion of PNNs can enhance recognition memory in adult mice (9-11), suggesting that PNNs comprise a critical regulatory component in normal learning and memory. Moreover, recent evidence suggests that PNNs may also have an important role in neuroprotection(12). PV neurons without a surrounding PNN are more vulnerable to oxidative stress(13) which has a knock-on effect on learning and memory(14). My hypothesis is that PNNs contribute substantially to adult learning and memory processes via two primary mechanisms (i) regulation of neuroplasticity and (ii) neuroprotection. My short-term objective is to test this hypothesis by degrading PNNs in cortical regions critical for learning, memory and behavioural control, and/or manipulating levels of oxidative stress via diet, exercise, or environmental enrichment, and then assessing the mice on cognitive tests dependent on those brain regions. We predict that performance on the tests will reflect a trade-off between increased synaptic plasticity and reduced neuroprotection, so may be improved or impaired depending on how the two types of manipulation are combined. In the long term, this research program will provide valuable insight into the mechanistic underpinnings of adult learning and memory processes, and how lifestyle factors including diet, exercise, and environmental enrichment can fundamentally alter both brain and behaviour.
神经科学中的一个新兴概念是,大脑的可塑性不仅取决于神经元和神经胶质,还取决于这些细胞外的结构。细胞外基质——约占大脑体积的20%(1),并有助于神经元和神经胶质的交流(2)——是这个角色的主要候选者。事实上,我的实验室最近的证据表明,一种被称为神经周围网络(PNN)的细胞外基质成分可能超出了它在神经发育中的既定作用,并有助于成人大脑的基本学习和记忆过程。本研究计划的首要目标是全面了解pnn参与成人认知的机制。pnn是细胞外基质的一个组成部分,主要包裹在抑制性小白蛋白阳性皮质神经元周围。pnn在发育过程中形成,并且在突触可塑性增强的关键时期的关闭中起着核心作用,从发育到成年期较低的水平(3)。酶降解硫酸软骨素蛋白聚糖(CSPGs)是PNNs的主要成分,可以重新开启成年大鼠眼优势可塑性的幼年关键期(3),并可以促进脊髓损伤和其他形式的神经系统损伤的恢复(4,5)。突触可塑性对于整个生命周期的学习和记忆也是必不可少的(6-8),然而,几乎没有研究pnn是否有助于成人大脑的基本学习和记忆过程。我的实验室最近的工作表明,pnn的消耗可以增强成年小鼠的识别记忆(9-11),这表明pnn在正常的学习和记忆中是一个关键的调节成分。此外,最近的证据表明,pnn也可能在神经保护中发挥重要作用(12)。没有周围PNN的PV神经元更容易受到氧化应激的影响(13),这对学习和记忆有连锁反应(14)。我的假设是,pnn通过两种主要机制(i)调节神经可塑性和(ii)神经保护,对成人的学习和记忆过程做出了重大贡献。我的短期目标是通过降解对学习、记忆和行为控制至关重要的皮层区域的pnn,和/或通过饮食、运动或环境富集来操纵氧化应激水平,然后在依赖于这些大脑区域的认知测试中评估小鼠,来验证这一假设。我们预测,在测试中的表现将反映突触可塑性增加和神经保护减少之间的权衡,因此可能会改善或损害取决于两种类型的操作如何结合。从长远来看,这个研究项目将为成人学习和记忆过程的机制基础以及包括饮食、锻炼和环境丰富在内的生活方式因素如何从根本上改变大脑和行为提供有价值的见解。

项目成果

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Saksida, Lisa其他文献

Saksida, Lisa的其他文献

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{{ truncateString('Saksida, Lisa', 18)}}的其他基金

The role of perineuronal nets in adult cognition
神经周围网在成人认知中的作用
  • 批准号:
    RGPIN-2019-06102
  • 财政年份:
    2022
  • 资助金额:
    $ 5.68万
  • 项目类别:
    Discovery Grants Program - Individual
The role of perineuronal nets in adult cognition
神经周围网在成人认知中的作用
  • 批准号:
    RGPIN-2019-06102
  • 财政年份:
    2020
  • 资助金额:
    $ 5.68万
  • 项目类别:
    Discovery Grants Program - Individual
The role of perineuronal nets in adult cognition
神经周围网在成人认知中的作用
  • 批准号:
    RGPIN-2019-06102
  • 财政年份:
    2019
  • 资助金额:
    $ 5.68万
  • 项目类别:
    Discovery Grants Program - Individual

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神经周围网络在甲基苯丙胺引起的额叶下垂和认知缺陷中的作用
  • 批准号:
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Defining the role of perineuronal nets in Alzheimer's Disease pathology
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    10753758
  • 财政年份:
    2023
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The role of perineuronal nets in adult cognition
神经周围网在成人认知中的作用
  • 批准号:
    RGPIN-2019-06102
  • 财政年份:
    2022
  • 资助金额:
    $ 5.68万
  • 项目类别:
    Discovery Grants Program - Individual
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神经活动和神经周围网络在青少年间歇性乙醇引起的社交焦虑中的作用
  • 批准号:
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Role of Neural Activity and Perineuronal Nets in Adolescent Intermittent Ethanol-Induced Social Anxiety
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  • 批准号:
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  • 财政年份:
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神经周围网络的分子结构
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神经周围网在癫痫中的作用
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  • 财政年份:
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  • 资助金额:
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