Novel approaches for interrogating and manipulating synaptic function, structure and plasticity

询问和操纵突触功能、结构和可塑性的新方法

• 批准号: 10391457
• 负责人: Matthew J Kennedy
• 金额: $ 53.36万
• 依托单位: UNIVERSITY OF COLORADO DENVER
• 依托单位国家: 美国
• 财政年份: 2020
• 资助国家: 美国
• 起止时间: 2020-05-01 至 2028-04-30
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10391457
• 关键词: Address; Biochemistry; Brain; Brain Diseases; Cellular biology; Communication; Development; Goals; Information Storage; Knowledge; Learning; Link; Memory; Modification; Molecular; Neuraxis; Neuronal Plasticity; Neurons; Shapes; Structure; Synapses; Synaptic plasticity; Time; Work; cognitive function; experimental study; in vivo; novel strategies; relating to nervous system; remote control; synaptic function; tool

Synapses throughout the central nervous system are sculpted by neural activity through changes in their size, shape and molecular composition, which either strengthen or weaken communication between neurons. This “plasticity” in synapse function is widely viewed as the central mechanism for information storage in the brain. While many forms of synaptic plasticity have been discovered and their molecular mechanisms intensely investigated, in many cases there is surprisingly little direct evidence linking them to the cognitive functions they are proposed to control. This has remained a challenge due to a lack of tools for rapidly and locally switching on or off the requisite biochemistry and cell biology underlying different plasticity mechanisms in real time, in vivo. We are developing new tools that fill this void with the long- term goal of addressing fundamental gaps in our knowledge concerning how synapses are modified at the molecular level through development and plasticity, how these modifications influence synapse/circuit function and ultimately the relevance of these mechanisms for important cognitive functions like learning and memory.

整个中枢神经系统的突触是由神经活动塑造的， 它们的大小、形状和分子组成的变化， 神经元之间的通信突触功能的这种“可塑性”被广泛认为是 大脑中储存信息的中枢机制。虽然许多形式的突触可塑性 在许多情况下， 令人惊讶的是，几乎没有直接证据将它们与它们的认知功能联系起来， 建议控制。这仍然是一个挑战，因为缺乏工具， 打开或关闭不同可塑性背后的必要生物化学和细胞生物学 在体内真实的时间里的机制。我们正在开发新的工具来填补这一空白， 长期的目标是解决我们关于突触是如何被激活的知识中的根本空白。 通过发育和可塑性在分子水平上进行修饰，这些修饰是如何 影响突触/电路功能，并最终这些机制的相关性， 重要的认知功能比如学习和记忆