权益分类	功能权益	普通用户	{{item.name}}会员
{{category.name}}	{{benefitItem.name}}

Plasticity of Functional Networks in Auditory Cortex

听觉皮层功能网络的可塑性

基本信息

批准号：
10434666
负责人：
Travis Austin Babola
金额：
$ 6.98万
依托单位：
JOHNS HOPKINS UNIVERSITY
依托单位国家：
美国
项目类别：
财政年份：
2021
资助国家：
美国
起止时间：
2021-07-01 至 2023-06-30
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/10434666
关键词：
3-Dimensional Address Adult Animals Auditory Auditory Perceptual Disorders Auditory area Auditory system Axon Behavior Behavioral Cells Cerebral Palsy Child Cochlear implant procedure Complex Cortical Column Decision Making Detection Development Discrimination Ear Environment Exposure to Foundations Goals Hearing Hearing problem Image Imaging technology Impaired cognition Interneurons Language Long-Term Effects Maps Mediating Microscopy Minor Mus Nervous system structure Neurons Ocular dominance columns Opsin Optics Parvalbumins Pathway Analysis Patients Perception Play Population Role Schizophrenia Shapes Speech Speed Testing Thalamic structure Time Visual Cortex Visual system structure autism spectrum disorder awake brain cell cell type congenital deafness critical period designer receptors exclusively activated by designer drugs excitatory neuron experience experimental study functional plasticity genetic technology holographic stimulation improved outcome inhibitory neuron insight neural circuit neural network optogenetics response sound

项目摘要

PROJECT SUMMARY In the developing nervous system, millions of neurons coordinate and refine their connections to give rise to incredibly complex behavior, such as speech and language. These particular behaviors require the proper function of intricate networks within the auditory cortex. In this proposal, functional neural networks will be investigated using high-speed, volumetric imaging within cortical columns during tone-detection behavior in mice. In addition to characterizing these networks using state-of-the-art network analysis, whether or not these networks are sufficient to drive behavior will be tested by activating or silencing connected neurons with 3D holographic stimulation. Understanding how these networks function in normal adults will provide unique insight into how the auditory cortex functions as a decision-making unit and provide a basis for understanding what happens when these networks are disrupted. Another major goal of this proposal is to investigate network reorganization during the critical period, a remarkable period of plasticity during cortical development in which ocular dominance columns from in the visual cortex and tonotopic maps sharpen in the auditory system. Previous studies have observed that rearing animals in the presence of an intermittent tone during this period dramatically increases the cortical space devoted to that tone. Despite the enhanced response to that tone, animals had difficulty discriminating minor differences in tones played around the reared tone. Paradoxically, preliminary results from our lab indicate that tone rearing dramatically decreases the cortical space that responds to that tone. This proposal seeks to reconcile these differences with similar approaches as those described above, which allows for simultaneous imaging of hundreds to thousands of neurons within a volume, but in mice reared with intermittent tones during the critical period. Network analysis will uncover the extent of the reorganization and provide key insights into how cortical circuits responds to early environmental sounds. Lastly, this proposal seeks to investigate which cell types orchestrate circuit reorganization during the critical period. In the developing cortex, a developmentally transient group of cells located beneath the cortical plate seem poised to fulfill this function. These subplate neurons are interwoven into cortical circuits with local subplate-to-subplate, thalamocortical, and layer IV projections. Quite remarkably, these are the first neurons to respond to sound in the cortex (even before layer IV). To test if subplate neurons mediate cortical reorganization, chemo- and optogenetic approaches will be used to silence and activate these cells during the critical period. Subsequent analysis of functional networks will be performed using volumetric imaging. Understanding the mechanisms that reorganize these circuits may provide insight into developmental causes of dysfunctional wiring that arise during this period and offer clues about how to restore plasticity in adult auditory circuits, which may improve outcomes of cochlear implantation in older, congenitally deaf patients.

项目总结