Plasticity of Functional Networks in Auditory Cortex

听觉皮层功能网络的可塑性

• 批准号: 10314817
• 负责人: Travis Austin Babola
• 金额: $ 6.64万
• 依托单位: JOHNS HOPKINS UNIVERSITY
• 依托单位国家: 美国
• 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/10314817
• 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

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.

项目摘要 在发展中的神经系统中，数以百万计的神经元协调并完善其连接以提供 出现令人难以置信的复杂行为，例如语音和语言。这些特殊的行为需要 在听觉皮层中复杂网络的正确功能。在此建议中，功能性神经网络将 可以在音调检测行为中使用高速，体积成像进行研究 老鼠。除了使用最先进的网络分析来表征这些网络外 网络足以通过激活或沉默的3D激活或沉默连接的神经元来测试行为 全息刺激。了解这些网络在正常成年人中的功能将如何提供独特的 深入了解听觉皮层如何作为决策单元的功能，并提供理解的基础 这些网络被破坏时会发生什么。 该提案的另一个主要目标是调查关键时期的网络重组，一个 在皮质发育过程中，可塑性的显着时期，其中眼部优势柱来自 视觉皮层和吨位图在听觉系统中锐化。先前的研究观察到饲养 在此期间，在间歇性语调的情况下，动物大大增加了皮质空间 致力于这种语气。尽管对这种语气的反应增强了，但动物很难区分小调 音调的差异围绕饲养的音调发挥作用。矛盾的是，我们实验室的初步结果表明 音调饲养大大降低了对这种音调的响应的皮质空间。该提议试图 将这些差异与上述相似的方法调和，这可以同时进行 在一卷中成像数百至数千个神经元，但在小鼠中以间歇性音调在 关键时期。网络分析将揭示重组的程度，并为 皮质电路如何响应早期的环境声音。 最后，该提案旨在调查哪种细胞类型在此期间协调电路的重组 关键时期。在发育中的皮质中，位于皮质下方的一组发育瞬态的细胞组 盘子似乎准备实现此功能。这些子板神经元与局部交织在一起 子板到纸板，丘脑皮质和第四层投影。非常重要的是，这些是第一个的神经元 响应皮层中的声音（甚至在第四层之前）。测试子板是否介导皮质 重组，化学和光遗传学方法将用于沉默和激活这些细胞。 关键时期。随后的功能网络分析将使用体积成像进行。 了解重组这些电路的机制可能会洞悉发展原因 在此期间出现的功能失调的接线，并提供有关如何恢复成人可塑性的线索 听觉电路可能会改善老年人，先天聋患者的人工耳蜗植入结果。