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: 9463646
• 负责人: Michele Insanally
• 金额: $ 9.25万
• 依托单位: NEW YORK UNIVERSITY SCHOOL OF MEDICINE
• 依托单位国家: 美国
• 财政年份: 2017
• 资助国家: 美国
• 起止时间: 2017-04-01 至 2019-09-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9463646
• 关键词: Acoustics; Address; Adult; Affect; Algorithms; Animals; Aphasia; Area; Attention; Auditory; Auditory Perception; Auditory area; Auditory system; Autistic Disorder; 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; Hearing; 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; cell cortex; detector; discount; dynamic system; experience; experimental study; flexibility; frontal lobe; 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.

项目概要/摘要 听觉系统经常面临为声音分配行为意义的任务： 婴儿立即引起您的注意，火警信号表明需要匆忙离开，而 熟悉的手机声音会导致提前退出会议，大脑是如何做到这一点的？ 看似毫不费力的壮举？大脑中的区域网络与听觉感知行为有关，但是 即使是被认为主要与声音表示有关的区域也有看起来像的细胞 这些“名义上无反应的细胞”对行为相关的声学输入无动于衷。 普遍存在，但尚未得到充分探索，可能为大脑如何完成与听觉相关的任务提供重要见解 例如，有新的证据表明这些细胞很重要。 用于生成对这些广泛观察到的但灵活的行为的系统级理解。 很少分析的神经元对于将听觉相关行为与听觉神经活动联系起来至关重要 途径，并可能对人工耳蜗 (CI) 用户的康复策略产生重要见解 刺激会导致高度可变的皮质激活。 该提案将研究名义上无反应的细胞在听觉感知行为中所扮演的角色 通过从听觉皮层（听觉皮层的下游区域（额叶的听觉域）进行记录和解码 皮层）和行为过程中的上游区域（听觉丘脑的内侧膝状核）。 该提案利用了老鼠行为的尖端电生理记录、光遗传学和一种新颖的方法 用于评估具有复杂反应曲线的细胞的单次试验解码算法，以解决以下问题 目标：表征名义上无反应的听觉皮层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着听觉表示和调节 名义上无反应的神经元的通路（目标 2）并确定名义上无反应的神经元的活动如何； 反应神经元动态地反映声音的行为意义（目标 3）。 将为动物如何计算声音的行为意义提供重要的见解。 每个听觉站在产生听觉相关行为中所扮演的特定角色将对（1）产生影响 改善疾病或损伤引起的听力缺陷的诊断和治疗，以及（2）改善听觉 刺激多个大脑区域以增强听觉感知的假肢装置。 经验丰富的导师和合作者团队将为候选人的短期和合作提供至关重要的培训 长期成功，包括：长期记录、光遗传学、LFP 分析和单试验解码器。 拟议的培训计划结合了实践培训、指导、课程作业、研讨会和专业培训 从长远来看，这种支持将使候选人能够领导一个将分析和分析相结合的实验室。 系统方法来探索名义上无反应活动对听觉行为的作用。