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意义

• 批准号: 10634831
• 负责人: Michele Insanally
• 金额: $ 7.66万
• 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/10634831
• 关键词: Acoustics; Adaptive Behaviors; Address; Animals; Attention; Auditory; Auditory Perception; Auditory Prosthesis; Auditory area; Auditory system; Behavior; Behavioral; Brain; Cells; Cellular Phone; Central Auditory Processing Disorder; Clinical; Cochlear Implants; Computer Systems; Diagnosis; Disease; Electrophysiology (science); Environment; Fire - disasters; Goals; Infant; Injury; Learning; Life; Locomotion; Measures; Neurons; Perception; Perceptual learning; Play; Population; Process; Prosthesis; Rattus; Role; Signal Transduction; System; Treatment Efficacy; Work; auditory pathway; computerized tools; experimental study; flexibility; hearing impairment; improved; in vivo; insight; meetings; optogenetics; rehabilitation strategy; relating to nervous system; sound; targeted treatment

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.

听觉系统经常被赋予声音行为意义的任务所挑战：一种声音的叫声 婴儿立即引起你的注意，火警发出需要匆忙离开的信号，熟悉的 你的手机铃声会让你提早退出会议。大脑似乎是如何做到这一点的 毫不费力的壮举？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示有关的细胞似乎对 与行为相关的声学输入。这些“名义上没有反应的细胞”非常普遍， 对大脑如何完成与听觉相关的学习和学习提供了关键的见解 将试镜与情景联系起来。例如，有新的证据表明，这些细胞对生成 灵活的行为。发展对这些被广泛观察但很少分析的系统级别的理解 神经元是将听觉相关行为与听觉通路中的神经活动联系起来所必需的，并可能产生 对于人工耳蜗(CI)使用者的康复策略的关键见解，因为CI刺激可以导致高度 可变的皮质激活。 这项提议将研究名义上无反应的细胞是如何出现和进化超过听觉学习的 在中枢听觉通路中构建灵活的神经元表征。我的目标是剖析当地的和长期的- 调节学习过程中名义上的非响应活动的范围电路动力学，并了解这些 动力学开启了听觉学习和感知的大门。这项提议利用了尖端的电生理学 记录大鼠的行为，光遗传操作和计算工具，以解决以下目标： 确定学习过程中听觉回路在中枢听轴中的调制方式(目标2)。结果是 这项工作将为动物如何处理具有行为意义的声音和 在行为具有挑战性的环境中保持灵活性。澄清每个听觉站点的具体作用 在产生适应行为方面的发挥将对改善听力的诊断和治疗有意义 疾病或损伤造成的缺陷，以及增强听觉感知的听觉假体装置。在……里面 在这些情况下，我们缺乏临床证明的方法来衡量高度可变的神经元的活动是否正常， 这使得在神经层面上判断治疗的有效性具有挑战性。确定关联性和 利用这一大群高度可变的细胞进行听觉学习和感知是这项研究的目标 求婚。

项目成果

Long-term recording reliability of liquid crystal polymer µECoG arrays.

• DOI: 10.1088/1741-2552/aae39d
• 发表时间: 2018-12
• 期刊: Journal of neural engineering
• 影响因子: 4
• 作者: Woods V;Trumpis M;Bent B;Palopoli-Trojani K;Chiang CH;Wang C;Yu C;Insanally MN;Froemke RC;Viventi J
• 通讯作者: Viventi J