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

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的大脑可塑性，成年人，和老化的大脑。我未来五年的研究计划分为三个主轴，每个主轴都专注于研究影响大脑可塑性的特定因素。这些实验旨在将联合收割机最先进的体内电生理学、化学和光遗传学、行为学、药理学和组织学结合在大鼠初级听觉皮层（A1）中，这是一个研究大脑可塑性的强大系统。 轴心岛确定如何感觉输入特性调节可塑性的发展，成人，和老化A1。我们以前已经证明，在环境中的听觉输入模式的存在是必要的成熟的A1电路在功能和结构水平。我们还表明，长期缺乏这样的模式在成年生活中可以诱导可塑性在成人A1，并最终导致不稳定的听觉皮层地图。本研究轴的主要目标是精确地确定声音输入特性，在质量和数量上，这是必要的，以诱导A1成熟在发展过程中或诱导可塑性成熟A1。第二轴确定发育、成年和衰老大鼠中小清蛋白阳性（PV+）神经元和生长抑素阳性（SOM+）神经元对A1可塑性的贡献。有大量的工作表明，无论是在早期发育，在成年期，和衰老过程中，皮质抑制在调节皮质可塑性的重要性。例如，CP的关闭需要皮层抑制的增加。轴II的主要重点是确定如何抑制性中间神经元，特别是PV+和SOM+细胞，参与皮质可塑性的调节，以及它们如何与年龄相关的地图不稳定。我们还将确定操纵这些细胞的活动是否可以使衰老大脑的可塑性调节正常化。轴III：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被重新用于处理其他感官输入。由于未知的原因，这个过程被称为跨模态可塑性显示出很大的个体间差异。在这项研究轴，我们的目标是确定在大鼠模型的感觉剥夺如何不同水平的听觉丰富和感觉经验调制的crossmodal接管的传入皮层。 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觉体验调节大脑可塑性的方式的新的深入理解，并可能有助于开发新的基于神经可塑性的治疗策略。

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.