Emergence of activity patterns in the cerebral cortex and their influence on brain circuit development and function

大脑皮层活动模式的出现及其对脑回路发育和功能的影响

• 批准号: 10495193
• 负责人: Linda J Richards
• 金额: $ 110.02万
• 依托单位: WASHINGTON UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2021
• 资助国家: 美国
• 起止时间: 2021-09-30 至 2026-08-31
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10495193
• 关键词: Address; Adult; Affect; Animals; Area; Behavior; Behavioral; Behavioral Assay; Birth; Brain; Calcium; Cells; Cerebral cortex; Complex; Development; Electroporation; Embryo; Ensure; Fatty acid glycerol esters; Fire - disasters; Human; Image; Instruction; Knowledge; Learning; Life; Link; Longevity; Longitudinal Studies; Mammals; Marsupialia; Mediating; Modeling; Modernization; Molecular; Mothers; Mus; Neurons; Pattern; Phase; Pregnancy; Process; Psyche structure; Reaction; Research; Rodent; Sensory; Shapes; System; Tail; Technology; Therapeutic Intervention; Travel; Visual system structure; Work; awake; behavioral outcome; calcium indicator; cell type; experience; experimental study; fetal; functional outcomes; imaging capabilities; in vivo; neural circuit; novel strategies; pup; relating to nervous system; serial imaging; therapeutic evaluation; tool

Project Summary/Abstract Brain function requires coordinated activation of specific networks engaged in systems that process information in localised and distributed manners. In order to develop such specific networks, the brain engages groups of neurons that fire together in ensembles that can be observed with calcium imaging. Patterns of spontaneous activity in the cerebral cortex are thought to enable the formation of circuits specialised for processing different types of sensory information. How the brain first switches on activity across areas is unknown. I propose to investigate exactly how and when in fetal life these patterns first occur in vivo, what regulates their development, and how they shape neural circuits and later brain function. A major barrier to addressing this question has been that patterns of activity such as patchwork-type activity in S1 and travelling waves in V1 are present at birth in rodents making it difficult to study this question in vivo as the brain apparently switches on before birth. To address this, I propose to apply modern scientific tools and technologies to an Australian marsupial mammal: the fat-tailed dunnart (S. crassicaudata; Dasyuridae), thereby developing a new approach for investigating brain development. Dunnarts are small (adults weigh ~15g), carnivorous animals whose pups (joeys) are born at an equivalent stage of development to embryonic day 10 in mouse or seven-week gestation in humans, and therefore most of their brain development occurs as they develop inside their mother's pouch. Despite this more primitive developmental phase, dunnarts have a six-layered cerebral cortex which is similar to a mouse but with advantageous exceptions such as a more advanced binocular visual system. Dunnarts are also able to solve complex configurable problems and learn quickly. To ensure feasibility of this project, I provide evidence that we can use targeted electroporation to introduce sensitive calcium indicators such as GCaMP6S into the cortex. In preliminary experiments we find that patchwork-type activity in S1 and traveling waves in V1 are evolutionarily conserved in dunnarts, motivating this new direction of my research to understand the development and function of these patterns of spontaneous activity. Having access to study the entire genesis and development of these patterns enables longitudinal studies that can link cells, circuits and behavior/function. The creation of longitudinal imaging capabilities bridging micro/meso/macro scales as well as awake behavior across the lifespan will be required in order to identify which neuronal cell types initiate spontaneous synchronous activity and whether these activity patterns are instructive in forming functionally-specific circuits. I will also explore how spontaneous activity in the cortex evolves throughout life as circuits begin to function to mediate sensory experience and behavioural reactions. I ensembles knowledge propose that by understanding the fundamental processes r equired to build of patterned activity in the brain and how these affect behavior, this work will advance our of the neural basis of mental experience.

项目总结/摘要 大脑功能需要特定网络的协调激活，这些网络参与处理 以本地化和分布式方式提供信息。为了发展这种特定的网络，大脑 这些神经元群在钙离子成像中可以被观察到。 大脑皮层的自发活动模式被认为是形成回路的基础 专门处理不同类型的感官信息。大脑是如何首先在大脑活动中 地区不详。我建议调查究竟如何以及何时在胎儿生活中这些模式第一次出现在体内， 是什么调节了它们的发育，以及它们如何塑造神经回路和后来的大脑功能。一个主要障碍 解决这个问题的方法是，S1和S2中的活动模式，如拼凑型活动， V1中的行波在啮齿动物出生时就存在，使得难以在体内研究这个问题， 大脑显然在出生前就开启了。为了解决这个问题，我建议应用现代科学工具， 澳大利亚有袋类哺乳动物：肥尾邓纳特（S。厚尾类;毛尾科）， 从而为研究大脑发育开辟了一条新途径。Dunnarts很小（成年人体重 约15克），食肉动物，其幼仔（乔伊）出生时的发育阶段与胚胎发育阶段相当 小鼠的第10天或人类的妊娠7周，因此它们的大部分大脑发育发生在 它们在母亲的育儿袋里发育尽管这是一个更原始的发育阶段， 六层大脑皮层，类似于小鼠，但有一些有利的例外，例如 先进的双目视觉系统。Dunnarts还能够解决复杂的可配置问题， 快为了确保这个项目的可行性，我提供了证据，我们可以使用靶向电穿孔， 将敏感的钙指标如GCaMP 6S引入皮质。在初步实验中，我们发现 S1中的拼块型活动和V1中的行波在Dunnarts中是进化上保守的， 这激发了我研究的新方向，以了解这些模式的发展和功能， 自发活动有机会研究这些模式的整个起源和发展， 纵向研究，可以连接细胞，电路和行为/功能。纵向成像的创建 在整个生命周期内，将需要连接微观/中观/宏观尺度以及清醒行为的能力 为了确定哪些神经元细胞类型启动自发同步活动，以及这些细胞是否 活动模式在形成功能特定的电路中是有益的。我也会探索 随着回路开始起调节感觉体验的作用， 行为反应。我 合奏 知识 我建议通过理解构建所需的基本过程 研究大脑中的模式化活动以及这些活动如何影响行为，这项工作将推动我们的研究。 精神体验的神经基础。