Selective dissection of local and distributed neocortical inhibitory circuits underlying sensory representation

感觉表征基础上的局部和分布式新皮质抑制电路的选择性解剖

• 批准号: 10867859
• 负责人: Emmanuel Luis Crespo
• 金额: $ 4.06万
• 依托单位: CENTRAL MICHIGAN UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2022
• 资助国家: 美国
• 起止时间: 2022-07-01 至 2024-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10867859
• 关键词: Address; Adult; Anesthesia procedures; Area; Automobile Driving; Behavior; Behavioral; Biological; Brain; Cells; Childhood; Cognitive; Communication; Complement; Complex; Data; Detection; Development; Developmental Process; Dissection; Doctor of Philosophy; Early Intervention; Electrophysiology (science); Engineering; Environmental Risk Factor; Equilibrium; Esthesia; Etiology; Genes; Genetic; Goals; Hyperactivity; Hypersensitivity; Image; Immunologic Factors; Interneurons; Intervention; Learning; Life; Link; Maps; Mediating; Mental disorders; Mentors; Molecular; Motion; Mus; Neocortex; Neurodevelopmental Disorder; Neurologic; Phase; Population; Postdoctoral Fellow; Predisposition; Prefrontal Cortex; Principal Investigator; Process; Property; Proteins; Reporting; Research; Research Personnel; Research Project Grants; Rewards; Role; Sensory; Sensory Process; Social Behavior; Social Interaction; Specificity; Syndrome; Task Performances; Technology; Testing; Training; Vibrissae; Water; Work; autism spectrum disorder; autistic children; behavioral phenotyping; brain shape; cell type; clinical diagnostics; density; diagnostic criteria; extracellular; hippocampal pyramidal neuron; in vivo; inhibitory neuron; insight; neocortical; nervous system disorder; neural; neural circuit; neurophysiology; next generation; novel; optogenetics; postnatal development; recruit; sensor; sensory cortex; sensory integration; social attachment; social deficits; therapeutic target; tool; tool development; two-photon; voltage

PROJECT SUMMARY/ABSTRACT The research proposed here is aimed at furthering our understanding of causal relationships between early neural circuit formation and adult behavior, and specifically how healthy brain development can go awry to result in deficits in sensory processing across a lifetime. Towards a deeper understanding of normal and aberrant neurodevelopmental processes, there is a critical need to deconstruct the driving pathophysiological mechanisms between developmental cortical hyperactivity and emergence of persistent maladaptive cognitive, sensory and social behaviors. Without such information, the promise of novel targets for early intervention in neurodevelopmental diseases will likely remain limited. During the F99 Phase, I will test if developmental hyperexcitation of pyramidal neurons leads to persistent adult hypersensitivity (Aim IA) and deficits in fast-spiking inhibitory neuron recruitment (Aim IB)—key neurophysiological and behavioral signatures seen in autism spectrum disorders and neurodevelopmental syndromes. In Aim II, I will complement my neurophysiological training in high density electrophysiological recordings and perform two-photon imaging of prefrontal cortex projections into sensory areas to test how they influence encoding and circuit dynamics regulated by local inhibitory neuron subtypes. This work will contribute to understanding the neurodevelopmental origins of hypersensitivity and will help to broaden our understanding of disturbances in spontaneous activity beyond genetic, immune and environmental factors by providing mechanistic insight into causal cell-type specific roles of pyramidal neuron and inhibitory neuron subtypes. The training for the F99/K00 Phases will complement my deep background in developing molecular technologies to dissect neocortical local and long-range projections driving complex behavior. In my own lab I will readily develop next-generation molecular technologies for dissecting neocortical computations across temporal and spatial scales with increasing biological complexity (genes, proteins, cells, circuits) underlying sensory processing.

项目总结/文摘