The significance of nominally non-responsive neural dynamics in auditory perception and behavior.

名义上无反应的神经动力学在听觉感知和行为中的重要性。

• 批准号: 10208850
• 负责人: Michele Insanally
• 金额: $ 24.9万
• 依托单位: UNIVERSITY OF PITTSBURGH AT PITTSBURGH
• 依托单位国家: 美国
• 财政年份: 2020
• 资助国家: 美国
• 起止时间: 2020-06-01 至 2023-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10208850
• 关键词: Acoustics; Address; Adult; Affect; Algorithms; Animals; Aphasia; Area; Attention; Auditory; Auditory Perception; Auditory Prosthesis; Auditory area; Auditory system; Behavior; Behavioral; Brain; Brain region; Caenorhabditis elegans; Cells; Cellular Phone; Central Auditory Processing Disorder; Chronic; Cochlear Implants; Cognition; Communication impairment; Complex; Diagnosis; Disease; Dyslexia; Electrophysiology (science); Environment; Female; Fire - disasters; Geniculate body structure; Impairment; Infant; Injury; Laboratories; Language Development; Lead; Learning; Life; Literature; Measures; Medial; Mentors; Mentorship; Modeling; Monitor; Monkeys; Names; Neurons; Pathologic; Pathway interactions; Perception; Play; Population; Prevalence; Prosthesis; Rattus; Reversal Learning; Role; Sensory; Signal Transduction; Stimulus; System; Techniques; Testing; Time; Training; Training Programs; Work; analytical method; auditory pathway; auditory processing; auditory thalamus; autism spectrum disorder; cell cortex; detector; discount; dynamic system; experience; experimental study; flexibility; frontal lobe; hearing impairment; improved; insight; male; meetings; neuromechanism; novel; optogenetics; rehabilitation strategy; relating to nervous system; response; sound; success; targeted treatment; vigilance

Project Summary / Abstract The auditory system is often challenged with the task of assigning behavioral meaning to sounds: the cry of an infant immediately commands your attention, a fire alarm signals the need for a hasty departure, and the familiar sound of your cell phone causes an early exit from a meeting. How does the brain accomplish this seemingly effortless feat? A network of regions in the brain are implicated in the act of auditory perception, but even regions thought to be primarily concerned with the representation of sounds have cells that seem unmoved by the behaviorally-relevant acoustic inputs. These “nominally non-responsive cells” are highly prevalent, underexplored, and may provide key insights into how the brain accomplishes auditory-related learning and contextualizes audition. For example, there is emerging evidence that these cells are important for generating flexible behaviors. Developing a systems-level understanding of these widely observed but rarely analyzed neurons is essential for relating auditory-related behavior to neural activity in the auditory pathway and may yield critical insights into rehabilitation strategies for cochlear-implant (CI) users as CI stimulation can result in highly variable cortical activation. This proposal will investigate the role nominally non-responsive cells play in auditory perceptual behaviors by recording and decoding from auditory cortex, an area downstream (an auditory domain of the frontal cortex), and an area upstream (the medial geniculate nucleus of the auditory thalamus) during behavior. This proposal leverages cutting-edge electrophysiological recordings in behaving rats, optogenetics, and a novel single-trial decoding algorithm for evaluating cells with complex response profiles to address the following aims: characterize the contribution of nominally non-responsive auditory cortical neurons to auditory behavior (Aim 1); determine how auditory behavioral variables are represented and modulated along the auditory pathway by nominally non-responsive neurons (Aim 2); and determine how the activity of nominally non- responsive neurons dynamically reflects the behavioral meaning of sounds (Aim 3). The results from this work will provide significant insight into how animals compute the behavioral significance of sounds. Clarifying the specific role each auditory station plays in generating auditory-relevant behaviors will have implications for (1) improved diagnosis and treatment of hearing deficits caused by disease or injury and (2) improved auditory prosthetic devices that stimulate multiple brain regions to enhance auditory perception. An experienced team of mentors and collaborators will provide training critical for the candidate's short- and long-term success, including: chronic recordings, optogenetics, LFP analysis and single-trial decoders. The proposed training program combines hands-on training, mentorship, coursework, seminars, and professional meetings. In the long-term, this support will equip the candidate to lead a laboratory that merges analytical and systems approaches to explore the role of nominally non-responsive activity to auditory behavior.

项目摘要 /摘要 听觉系统通常会挑战将行为含义分配给声音的任务： 婴儿立即引起您的注意，火警警报表明需要匆忙出发，而 熟悉的手机声音会引起会议的早期出口。大脑如何完成此操作 看似轻松的壮举？在听觉感知的行为中实现了大脑中的区域网络，但 甚至被认为主要涉及声音的表示的区域都具有细胞 与行为相关的声学输入不为所动。这些“名义上无反应性细胞”高度高 普遍，不充分散布，并且可能会提供有关大脑如何完成听觉相关的关键见解 学习和上下文化试镜。例如，有新的证据表明这些细胞很重要 用于产生灵活的行为。对这些广泛观察到的系统级别的理解，但 很少分析的神经元对于将听觉相关的行为与听觉中的神经元活动联系起来至关重要 途径，可能会为人工耳蜗（CI）用户提供对康复策略的关键见解 刺激会导致高度可变的皮质激活。 该建议将调查名义上无反应性细胞在听觉感知行为中起的作用 通过从听觉皮层录制和解码，这是下游的区域（额叶的听觉域 在行为过程中，皮质）和一个区域（听觉丘脑的内侧遗传核）。 提案利用行为大鼠，光遗传学和一种新颖的尖端电生理记录 用于评估具有复杂响应曲线的细胞以解决以下细胞的单试算法 目的：表征名义上无反应性听觉的皮质神经元对听觉行为的贡献 （目标1）;确定听觉行为变量如何沿听觉表示和调制 名义上无反应性神经元的途径（AIM 2）；并确定名义上非 - 响应神经元动态反映声音的行为含义（AIM 3）。这项工作的结果 将为动物如何计算声音的行为意义提供重大见解。澄清 每个听觉站在生成听觉相关的行为中扮演的具体角色将对（1）产生影响 改善了疾病或受伤引起的听力缺乏的诊断和治疗，（2）改善了听觉 刺激多个大脑区域以增强听觉感知的假体设备。 经验丰富的导师和合作者团队将为候选人的短期和 长期成功，包括：慢性记录，光遗传学，LFP分析和单次试验解码器。这 拟议的培训计划结合了动手培训，指导，课程工作，半手级和专业人士 会议。从长远来看，这种支持将使候选人能够领导一个合并分析和合并的实验室 系统方法探索名义上无响应活动对听觉行为的作用。