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

项目摘要/摘要 听觉系统经常面临赋予声音行为意义的挑战：声音的叫声 婴儿立即引起你的注意，火警发出需要匆忙离开的信号，还有 熟悉的手机铃声会让你提早退出会议。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，但 即使是被认为主要关注声音表示的区域，也有似乎 对与行为相关的声音输入无动于衷。这些“名义上没有反应的细胞”是高度 普遍的，未被探索的，可能为大脑如何完成与听觉相关的任务提供了关键的见解 学习并将试镜融入情景中。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。发展对这些广泛观察到的但 很少被分析的神经元是将听觉相关行为与听觉中的神经活动联系起来的关键 途径，并可能产生关键的洞察力的康复策略的人工耳蜗(CI)使用者作为CI 刺激可导致高度可变的皮质激活。 这项建议将调查名义上无反应的细胞在听觉感知行为中所扮演的角色 通过从听觉皮质进行记录和解码，下游区域(额叶的听域 和上游区域(听觉丘脑的内侧膝状核)。这 该提案利用了尖端的电生理记录来表现大鼠的行为，光遗传学，以及一种新的 用于评估具有复杂响应曲线的细胞的单次尝试解码算法，以解决以下问题 目的：描述名义上无反应的听觉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节 名义上无反应神经元的通路(目标2)；并确定名义上无反应神经元的活动如何 反应神经元动态地反映声音的行为意义(目标3)。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。澄清 每个听觉站点在产生听觉相关行为方面所起的具体作用将对(1)产生影响。 改进疾病或损伤引起的听力障碍的诊断和治疗；(2)改善听力 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应聘者提供关键的短期和 长期的成功，包括：慢性录音、光遗传学、LFP分析和单次试用解码器。这个 建议的培训计划结合了实践培训、导师指导、课程作业、研讨会和专业培训 开会。从长远来看，这种支持将使候选人有能力领导一个将分析和 探索名义上对听觉行为无反应活动的作用的系统方法。

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.