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

项目概要/摘要 听觉系统经常面临着为声音赋予行为意义的任务： 一个婴儿立即引起你的注意，一个火警信号需要匆忙离开， 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？大脑中的一个区域网络与听觉感知有关， 即使是被认为主要与声音表征有关的区域， 不被行为相关的声学输入所动。这些“名义上无反应的细胞”是高度敏感的。 普遍存在，探索不足，并可能提供关键的见解，大脑如何完成与记忆有关的 学习并将听力置于情境中。例如，有新的证据表明，这些细胞是重要的 来产生灵活的行为。发展对这些广泛观察到但 很少分析的神经元对于将听觉相关行为与听觉中的神经活动联系起来至关重要。 途径，并可能产生关键的见解，为人工耳蜗植入（CI）用户的康复策略，作为CI 刺激可导致高度可变的皮层激活。 本计画将探讨名义上无反应细胞在听觉知觉行为中扮演的角色 通过记录和解码听觉皮层，下游区域（额叶的听觉域） 皮质）和上游区域（听觉丘脑的内侧膝状体核）。这 该提案利用了行为大鼠的尖端电生理记录，光遗传学和一种新的 用于评估具有复杂响应分布的细胞的单次试验解码算法，以解决以下问题 目的：研究名义上无反应的听皮层神经元对听觉行为的影响 (Aim 1）;确定听觉行为变量如何沿着听觉听觉表征和调制 途径的名义上无反应的神经元（目的2）;并确定如何活动的名义上无反应的神经元， 响应神经元动态地反映声音的行为意义（目的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要的见解。明确 每个听觉站在产生与听觉相关的行为中扮演的特定角色将对（1）产生影响 改善由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体装置。 经验丰富的导师和合作者团队将为候选人的短期和长期培训提供关键培训。 长期的成功，包括：慢性记录，光遗传学，LFP分析和单次试验解码器。的 拟议的培训计划结合了实践培训，指导，课程，研讨会和专业 会议.从长远来看，这种支持将使候选人能够领导一个将分析和 系统的方法来探索名义上的非响应活动的听觉行为的作用。

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.