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: 10261859
• 负责人: Linda J Richards
• 金额: $ 110.25万
• 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/10261859
• 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.

项目摘要/摘要 大脑功能需要协调激活参与系统的特定网络 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 结合成组的神经元一起放电，这可以用钙成像观察到。 大脑皮层自发活动的模式被认为能够形成电路 专门处理不同类型的感官信息。大脑是如何开始活动的 地区未知。我建议研究这些模式在胎儿生命中是如何以及何时在活体内首次发生的， 是什么控制了它们的发育，以及它们如何塑造神经回路和后来的大脑功能。一大障碍 要解决这个问题，一直是活动的模式，如S1和 V1中的行波在啮齿动物出生时就存在，这使得在体内研究这个问题变得困难，因为 显然，大脑在出生前就开启了。为了解决这个问题，我建议应用现代科学工具和 一种澳大利亚有袋哺乳动物的技术：大尾袋鼠(S.crassicaudata；Dasyuridae)， 从而开发了一种研究大脑发育的新方法。邓纳特人很小(成年人体重 ~15克)，肉食性动物，其幼崽(幼崽)出生时处于与胚胎相同的发育阶段 小鼠怀孕10天或人类怀孕7周，因此它们的大脑发育大部分发生在 它们在母亲的育儿袋内发育。尽管处于更原始的发育阶段，但笨蛋们有 六层大脑皮层，类似于小鼠，但有优势的例外，如更 先进的双目视觉系统。Dunnart还能够解决复杂的可配置问题并学习 快点。为了确保这个项目的可行性，我提供了证据，证明我们可以使用定向电穿孔来 将敏感的钙指示剂如GCaMP6S引入大脑皮层。在初步实验中，我们发现 在Dunnarts中，S1的拼接类型活动和V1的行波在进化上是保守的， 激励我的研究的这个新方向，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能够 可以将细胞、电路和行为/功能联系起来的纵向研究。纵向成像的产生 将需要连接微观/中观/宏观尺度以及整个生命周期的唤醒行为的能力 为了确定哪些神经细胞类型启动自发的同步活动，以及这些 活动模式对形成特定功能的回路很有指导意义。我还将探索如何自发地 大脑皮质的活动在整个生命过程中都在进化，因为电路开始发挥调节感觉体验和 行为反应。我 合唱团 知识 建议通过了解构建所需的基本流程 以及这些活动如何影响行为，这项工作将推动我们的 心理体验的神经基础。