Role of sensory experience in the regulation of plasticity in the developing, adult and aging brain

感官体验在发育、成人和衰老大脑可塑性调节中的作用

• 批准号: RGPIN-2019-04761
• 负责人: deVillersSidani, Etienne
• 金额: $ 3.42万
• 依托单位: McGill University
• 依托单位国家: 加拿大
• 项目类别: Discovery Grants Program - Individual
• 财政年份: 2022
• 资助国家: 加拿大
• 起止时间: 2022-01-01 至 2023-12-31
• 项目状态: 已结题
• 来源: https://www.nserc-crsng.gc.ca/ase-oro/Details-Detailles_eng.asp?id=761339
• 关键词: Role; sensory; experience; regulation; plasticity

The long-term objective of my research program is to determine how sensory experience modulates brain plasticity in the developing, adult, and aging brain. My research plan for the next five years is divided into three main axes, each focusing on investigating specific factors that influence brain plasticity. The experiments proposed to combine state-of-the-art in-vivo electrophysiology, chemo and optogenetics, behavior, pharmacology, and histology in the rat primary auditory cortex (A1), a powerful system to study brain plasticity. Axis I. Determining how sensory input characteristics regulate plasticity in the developing, adult, and aging A1. We have previously demonstrated that the presence of auditory input patterns in the environment was necessary for the maturation of A1 circuits both at a functional and structural level. We have also shown that a prolonged absence of such patterns during adult life can induce plasticity in the adult A1 and ultimately lead to destabilization of auditory cortical maps. The main objective of this research Axis is to determine precisely the sound input characteristics, in quality and quantity that are necessary to induce A1 maturation during development or to induce plasticity in the mature A1. Axis II. Determining the contribution of parvalbumin-positive (PV+) neurons and somatostatin-positive (SOM+) neuron to A1 plasticity in the developing, adult and, aging rat. There is extensive work showing the importance of cortical inhibition in the regulation of cortical plasticity, whether during early development, during adulthood, and aging. The closure of the CP, for example, requires an increase in cortical inhibition. The main focus of Axis II is to determine how inhibitory interneurons, particularly PV+ and SOM+ cells, participate in the regulation of cortical plasticity and how they are related to age-related map instability. We will also determine if manipulating the activity of these cells can normalize the regulation of plasticity in the aging brain. Axis III: Identifying the regulating mechanisms of cross-modal plasticity. It is now well established that the visual cortex of blind individuals is repurposed to process other sensory inputs. For unknown reasons, this process known as cross-modal plasticity displays substantial inter-individual variability. In this research Axis, our goal is to determine in rat models of sensory deprivation how various levels of auditory enrichment and sensory experience modulates the crossmodal takeover of the deafferented cortex. The integrative research plan I propose will provide a rich training environment for a minimum of 15 students over the next five years. The scientific outcomes we anticipate will bring a novel in-depth understanding of the way sensory experience regulates brain plasticity and are likely to contribute to the development of new neuroplasticity-based therapeutic strategies.

我的研究项目的长期目标是确定感官体验如何调节发育中、成年和衰老的大脑的可塑性。我未来五年的研究计划分为三个主轴，每个主轴都侧重于研究影响大脑可塑性的具体因素。本实验拟结合大鼠初级听觉皮层（A1）的活体电生理学、化学和光遗传学、行为学、药理学和组织学，A1是研究大脑可塑性的一个强大系统。轴1.确定感官输入特征如何调节发育、成人和衰老过程中的可塑性我们之前已经证明，环境中听觉输入模式的存在对于A1回路在功能和结构水平上的成熟是必要的。我们还发现，成年期长时间缺乏这种模式会导致成年A1的可塑性，并最终导致听觉皮层图的不稳定。本研究的主要目的是精确地确定声音输入的质量和数量特征，这些特征是在发育过程中诱导A1成熟或诱导成熟A1可塑性所必需的。轴II。确定小白蛋白阳性（PV+）神经元和生长抑素阳性（SOM+）神经元对发育、成年和衰老大鼠A1可塑性的贡献。有大量的研究表明皮层抑制在皮层可塑性调节中的重要性，无论是在早期发育、成年期还是衰老期间。例如，CP的关闭需要皮质抑制的增加。Axis II的主要重点是确定抑制性中间神经元，特别是PV+和SOM+细胞如何参与皮质可塑性的调节，以及它们如何与年龄相关的图谱不稳定性相关。我们还将确定操纵这些细胞的活动是否可以使老化大脑的可塑性调节正常化。轴三：识别跨模态可塑性的调节机制。现在已经确定盲人的视觉皮层是用来处理其他感官输入的。由于未知的原因，这种被称为跨模态可塑性的过程显示出大量的个体间变异性。在这项研究中，我们的目标是在感觉剥夺的大鼠模型中确定不同水平的听觉富集和感觉经验如何调节失传入皮层的跨模式接管。我提出的综合研究计划将在未来五年内为至少15名学生提供丰富的培训环境。我们预期的科学成果将带来对感官体验调节大脑可塑性方式的新颖深入的理解，并可能有助于开发新的基于神经可塑性的治疗策略。