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The Instruction of Sensory Inputs in Inhibitory Circuit Maturation in the Somatosensory Cortex

体感皮层抑制电路成熟中感觉输入的指令

基本信息

批准号：
10198716
负责人：
Rachel A Babij
金额：
$ 4.78万
依托单位：
WEILL MEDICAL COLL OF CORNELL UNIV
依托单位国家：
美国
项目类别：
财政年份：
2018
资助国家：
美国
起止时间：
2018-07-16 至 2022-05-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/10198716
关键词：
Agonist Animals Area Behavior Brain Calcium Cell physiology Cells Code Comprehension Data Development Developmental Process Disease Early Diagnosis Environmental Risk Factor Event Frequencies Functional disorder GABA-A Receptor Genes Genetic Genetic Predisposition to Disease Genetic Risk Goals Impairment Instruction Interneurons Investigation Knowledge Life Experience Link Mechanical Stimulation Modeling Morphology Movement Mus Neonatal Neurodevelopmental Disorder Neurons Neurophysiology - biologic function Neurosciences Outcome Output Pathogenesis Patients Pattern Perception Population Process Pyramidal Cells Research Role Sensory Sensory Deprivation Sensory Disorders Signal Transduction Social Interaction Somatosensory Cortex Synapses Synaptic Receptors System Techniques Testing Thalamic Nuclei Thalamic structure Time Vibrissae Viral Work anatomical tracing autism spectrum disorder cell type developmental disease excitatory neuron experience gamma-Aminobutyric Acid high risk hippocampal pyramidal neuron improved in vivo calcium imaging insight mouse model nerve supply neuronal circuitry novel patient population perinatal brain postnatal postnatal period presynaptic programs receptor recruit sensory input sensory stimulus tool translational impact two-photon

项目摘要

PROJECT SUMMARY/ABSTRACT Autism Spectrum Disorders (ASD) are a group of common neurodevelopmental disorders of diverse presentation, though sensory disturbances are consistently noted. Previous work has demonstrated a requirement for sensory input in the morphological maturation of subtypes of interneurons in the somatosensory cortex, but the effect this has on circuit activity and regional output is unknown. We hypothesize that sensory inputs recruit select interneuron subtypes to trigger the maturation of cortical circuits and that perturbations of this process cause lasting abnormalities in regional cortical output, which underlie the pathophysiology of neurodevelopmental disorders. To test our hypothesis, we will record the spontaneous network activity of subpopulations of neurons and in sensory deprived animals. We will identify the presynaptic inputs to these cells with an anatomical tracer. We will also utilize a mouse model of autism to reveal the function of a high-risk ASD gene in the maturation of circuits involving inhibitory interneurons and intracortical projection neurons. This investigation will fill a substantial gap in knowledge of ASD pathogenesis and the interaction between genetic background and activity-dependent developmental processes. The complete picture of ASD pathogenesis remains unclear. This project aims to describe how neuronal activity guides circuit development in the context of increased genetic risk, providing mechanistic insight into disease development and laying the groundwork for earlier diagnosis and novel treatment targets.

项目总结/文摘

项目成果

期刊论文数量（1）

专著数量（0）

科研奖励数量（0）

会议论文数量（0）

专利数量（0）

Assemblies of Perisomatic GABAergic Neurons in the Developing Barrel Cortex.

DOI：
10.1016/j.neuron.2019.10.007
发表时间：
2020-01-08
期刊：
Neuron
影响因子：
16.2
作者：
Modol L;Bollmann Y;Tressard T;Baude A;Che A;Duan ZRS;Babij R;De Marco García NV;Cossart R
通讯作者：
Cossart R