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

基本信息

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
项目类别：
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

项目摘要

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.

修改的项目摘要/摘要部分自发的活动模式被认为是对多种物种多个脑电路的组装和成熟的启发性。自发驱动的活动有望指导新生儿结构电路模板的形成，这反过来又影响了整个生命的新皮层功能。自发活动模式的干扰具有很大的临床相关性，因为它们有可能导致新皮层回路的永久性错误，这是神经发育和精神疾病的主要原因。因此，各种研究表明，新生儿发育过程中遗传和环境因素的干扰表现出神经发育和精神疾病的高风险。然而，关于活动的自发模式如何控制新皮层连通性的出现和维护，以及它最终如何影响体内电路功能。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性（例如视网膜波）对于建立精确的远距离和局部新皮层回路至关重要，并且当一级视觉皮质中的生命早期破坏了活性依赖性连接性时，视觉处理和认知功能就会改变。这些研究的理由是，它们将为神经发育和精神疾病中的新皮质功能障碍提供新的见解。具体目的是：1）评估自发活性在视觉皮层中新生儿基因表达的作用。 2）评估自发活动在视觉皮层突触连通性上的作用。 3）确定新生儿自发活动模式对以后年龄的视觉处理的影响。在第一个目标下，将进行单细胞RNA测序实验，以阐明自发活性如何影响新生儿时代的基因表达。在第二个目标下，将进行切片的电生理实验，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，以研究自发活性在视觉皮层的体内功能中的作用。该应用程序中提出的研究具有创新性，因为它将为研究新皮层的转录组学，连通性和体内功能的自发活动的作用开辟新的途径。拟议的研究之所以重要，是因为它将提供新的机械洞察力，以了解自发活动如何指导新生儿建筑电路模板的形成，这反过来又影响了整个生命的新皮层功能。