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

听觉系统经常面临着为声音赋予行为意义的任务： 婴儿立即命令你的注意力，火警信号需要匆忙离开，熟悉的 手机的声音会导致提前退出会议。大脑是如何做到这一点的 不费力的壮举？大脑中的一个区域网络与听觉感知行为有关，但即使是区域 被认为主要与声音的表达有关的细胞似乎不受声音的影响。 行为相关的声学输入。这些“名义上无反应细胞”非常普遍， 研究不足，并可能为大脑如何完成与记忆相关的学习提供关键见解， 情境化的试听。例如，有新的证据表明，这些细胞对产生 灵活的行为。发展对这些广泛观察但很少分析的系统级理解 神经元对于将听觉相关行为与听觉通路中的神经活动相关联是必不可少的， 人工耳蜗植入（CI）用户康复策略的重要见解，因为CI刺激可导致高度 不同的皮层激活 这项提议将研究如何名义上无反应细胞出现和进化的听觉学习， 在中枢听觉通路中构建灵活的神经元表征。我的目标是剖析本地和长期- 在学习过程中调节名义上无反应活动的范围电路动态，并发现这些 动态门听觉学习和感知。这项提案利用了尖端的电生理学 在行为大鼠中的记录、光遗传学操作和计算工具，以解决以下目的： 确定在学习过程中，听觉回路是如何在中央听觉轴中调制的（目标2）。结果 从这项工作将提供关键的见解，动物如何处理与行为意义的声音， 在行为上具有挑战性的环境中保持灵活。澄清每个听觉站的具体作用 在产生适应性行为方面的作用将对改善听力的诊断和治疗产生影响。 由疾病或损伤引起的缺陷以及听觉假体装置以增强听觉感知。在 在这些情况下，我们缺乏临床证明的措施，以确定高度可变的神经元的活动是否正常， 这使得在神经水平上判断治疗的功效具有挑战性。确定相关性和 将这种大量的高度可变的细胞用于听觉学习和感知是本发明的目标。 提议

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 how nominally non-responsive cells emerge and evolve over auditory learning to construct flexible neuronal representations in a central auditory pathway. I aim to dissect the local and long- range circuit dynamics that modulate nominally non-responsive activity during learning and discover how these dynamics gate auditory learning and perception. This proposal leverages cutting-edge electrophysiological recordings in behaving rats, optogenetic manipulation, and computational tools to address the following aim: Determine how auditory circuits are modulated in a central auditory axis during learning (Aim 2). The results from this work will provide critical insights into how animals process sounds with behavioral significance and remain flexible in behaviorally challenging environments. Clarification of the specific role each auditory station plays in generating adaptive behaviors will have implications for improving diagnosis and treatment of hearing deficits caused by disease or injury as well as auditory prosthetic devices to enhance auditory perception. In these cases, we lack clinically proven measures for whether the activity of highly variable neurons is normal, which makes judging the efficacy of treatments at the neural level challenging. Determining the relevance and utility of this large population of highly variable cells to auditory learning and perception is the goal of this proposal.