Role of spontaneous activity towards the assembly and function of neocortical circuits

自发活动对新皮质回路的组装和功能的作用

• 批准号: 10737253
• 负责人: Renata Batista-Brito
• 金额: $ 54.37万
• 依托单位: ALBERT EINSTEIN COLLEGE OF MEDICINE
• 依托单位国家: 美国
• 财政年份: 2023
• 资助国家: 美国
• 起止时间: 2023-09-01 至 2026-07-31
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10737253
• 关键词: Ablation; Action Potentials; Adolescent; Adult; Age; Architecture; Behavior; Brain; Cells; Cholinergic Receptors; Critical Pathways; Data; Development; Dimensions; Early Diagnosis; Electrophysiology (science); Environmental Risk Factor; Eye; Functional disorder; Gene Expression; Genetic; Genetic Transcription; Goals; Head; Impairment; In Vitro; Individual; Knowledge; Lateral Geniculate Body; Life; Maintenance; Measures; Mental disorders; Methodology; Molecular; Mus; Neocortex; Neonatal; Nervous System; Neurodevelopmental Disorder; Neurons; Pattern; Perception; Research; Retina; Role; Sensory; Shapes; Slice; Synapses; System; Testing; Thalamic structure; Therapeutic Intervention; V1 neuron; Vision; Visual; Visual Cortex; Visual System; Work; area striata; biomarker identification; cell type; cholinergic; clinically relevant; cognitive ability; cognitive function; experimental study; high risk; in vivo; innovation; insight; neocortical; neural circuit; neurotransmission; novel; postnatal; programs; public health relevance; segregation; single-cell RNA sequencing; superior colliculus Corpora quadrigemina; transcriptomics; visual information; visual processing

Modified Project Summary/Abstract Section Spontaneous patterns of activity is thought to be instructive for the assembly and maturation of multiple brain circuits across several species. Spontaneously driven activity is expected to guide the formation of a neonatal architectural circuit template, which in turn impacts neocortical function throughout life. Disturbances of spontaneous activity patterns have great clinical relevance, as they are liable to lead to permanent miswiring of neocortical circuits, a leading cause for neurodevelopmental and psychiatric disorders. Accordingly, various studies reveal that disturbances in genetic and environmental factors during neonatal development present high risk for neurodevelopmental and psychiatric disorders. Yet little is known about how spontaneous patterns of activity control the emergence and maintenance of neocortical connectivity, and how it ultimately impacts in vivo circuit function. Our goal is to understand how spontaneous patterns of network activity orchestrate the proper maturation and function of the visual cortex. The central hypothesis is that spontaneous neonatal activity, such as retinal waves, is critical for the establishment of precise long-range and local neocortical circuits, and that altered visual processing and cognitive functions develop when activity dependent connectivity is disrupted early in life in the primary visual cortex. The rationale for these studies is that they will provide novel insights into neocortical dysfunction in neurodevelopmental and psychiatric disorders. The specific aims are: 1) Assess the role of spontaneous activity on neonatal gene expression in the visual cortex. 2) Assess the role of spontaneous activity on visual cortex synaptic connectivity. 3) Determine the impact of neonatal spontaneous patterns of activity on visual processing at later ages. Under the first aim, single-cell RNA sequencing experiments will be performed in order to elucidate how spontaneous activity impact gene expression at neonatal ages. Under the second aim, slice electrophysiology experiments will be performed in order to elucidate how spontaneous activity impact synaptic maturation. Under the third aim, in vivo recordings will be performed in order to investigate the role of spontaneous activity for the in vivo function of the visual cortex. The research proposed in this application is innovative because it will open new avenues for studying the role of spontaneous activity for transcriptomics, connectivity, and in vivo function of the neocortex. The proposed research is significant because it will provide novel mechanistic insights into how spontaneous activity might guide the formation of a neonatal architectural circuit template, which in turn impacts neocortical function throughout life.

修改项目摘要/摘要部分 自发的活动模式被认为对几个物种的多个脑回路的组装和成熟具有指导意义。自发驱动的活动预计将引导新生儿架构电路模板的形成，这反过来又会影响整个生命过程中的新皮层功能。自发活动模式的紊乱具有很大的临床意义，因为它们容易导致新皮层回路的永久性错误布线，这是神经发育和精神疾病的主要原因。因此，各种研究表明，新生儿发育期间遗传和环境因素的干扰对神经发育和精神疾病具有高风险。然而，人们对自发活动模式如何控制新皮层连接的出现和维持，以及它最终如何影响体内电路功能知之甚少。我们的目标是了解网络活动的自发模式如何协调视觉皮层的适当成熟和功能。中心假设是自发的新生儿活动，如视网膜波，是建立精确的远程和局部新皮层回路的关键，并且当初级视觉皮层中的活动依赖连接在生命早期被破坏时，视觉处理和认知功能发生改变。这些研究的基本原理是，他们将提供新的见解，新皮质功能障碍的神经发育和精神疾病。具体目标是：1）评估自发活动对新生儿视皮层基因表达的作用。2)评估自发活动对视皮层突触连接的作用。3)确定新生儿自发活动模式对后期视觉处理的影响。在第一个目标下，将进行单细胞RNA测序实验，以阐明自发活动如何影响新生儿年龄的基因表达。在第二个目标下，将进行切片电生理学实验，以阐明自发活动如何影响突触成熟。在第三个目标下，将进行体内记录，以研究自发活动对视觉皮层体内功能的作用。本申请中提出的研究是创新的，因为它将为研究转录组学，连接性和新皮层体内功能的自发活动的作用开辟新的途径。这项研究意义重大，因为它将为自发活动如何引导新生儿架构电路模板的形成提供新的机制见解，从而影响整个生命过程中的新皮层功能。