Neural circuitry for flexible control of auditory perception and behavior

用于灵活控制听觉感知和行为的神经回路

基本信息

批准号：
9013994
负责人：
Kishore V Kuchibhotla
金额：
$ 11.99万
依托单位：
NEW YORK UNIVERSITY SCHOOL OF MEDICINE
依托单位国家：
美国
项目类别：
财政年份：
2015
资助国家：
美国
起止时间：
2015-12-01 至 2017-11-30
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/9013994
关键词：
Accelerometer Acetylcholine Acoustics Address Adult Animals Area Attention Auditory Auditory Perception Auditory area Auditory system Autistic Disorder Awareness Axon Basal Nucleus of Meynert Behavior Behavioral Brain Brain region Calcium Cells Communication Complex Consultations Data Dependence Disease Disinhibition Elements Equilibrium Genetic Hearing Human Image Interneurons Laboratories Language Development Language Development Disorders Language Disorders Lead Learning Logic Mediating Mentors Mentorship Modeling Monitor Mus Music Nature Neuronal Plasticity Neurons Output Pathology Patients Pattern Perceptual learning Play Population Post-Traumatic Stress Disorders Probability Process Publishing Recruitment Activity Research Personnel Reversal Learning Rewards Role Sensory Shapes Signal Transduction Social Interaction Speech Stimulus Synapses System Testing Therapeutic Time Training Training Programs Weight Whole-Cell Recordings Work base behavioral response cholinergic excitatory neuron experience feeding flexibility in vivo in vivo imaging inhibitory neuron meetings memory retrieval movie neural circuit neuroregulation optogenetics public health relevance relating to nervous system research study response sound spatiotemporal success treatment strategy two-photon voltage clamp

项目摘要

DESCRIPTION (provided by applicant): The mammalian auditory system can be modified by experience and by behavioral context. This is an important feature of the primary auditory cortex (A1), especially in forming representations of sensory signals such as speech, music and other forms of acoustic communication. With time and experience, animals can learn that specific sounds and not others can signal rewards. Moreover, animals can also learn that the same sound in different contexts requires distinct behavioral responses. In humans, for example, the sound of a gunshot heard on the street versus during a movie will likely lead to divergent behavioral responses. Conversely, PTSD patients hear a loud bang and may be unable to make the same differentiation. Such deficits are also implicated in developmental and language disorders including autism. Understanding the mechanisms of perceptual flexibility is thus essential for studies of normal or pathological auditory processing. Classically, sensory information was thought to be processed in a linear manner where each successive brain area extracts more complex features and then transmits this to higher-order areas that confer meaning (feed-forward processing). However, in the auditory cortex, this model is increasingly challenged by neural recordings in behaving animals in which context or behavioral state plays an important role in modulating neuronal activity. What happens during behavioral conditions where the same sound draws attention in one context (active context) but does not require attention in another (passive context)? The preliminary data in this proposal shows that auditory cortical neurons have distinctly different activity patterns in those two contexts. The precise mechanisms that govern this context-dependent activity in auditory cortex remain unknown. Neuromodulatory centers involved in attention may play a critical role in context-switching, given their importance in long-term plasticity and learning. This proposal will test the hypothesis that context- dependence in auditory cortex arises because long-range attentional signals directly act on local circuits. First, experiments will be conducted to test whether synaptic inputs, the building blocks of neuronal activity, are different in auditory cortex in both contexts (Aim 1). Second, experiments will test whether acetylcholine- releasing projections from the nucleus basalis, a brain region involved in attention, are naturally active during the active task and directly alter the synaptic weights in auditory cortex (Aim 2). Third, experiments will test how context-dependent activity emerges over the course of learning by looking at both the attentional signal from the nucleus basalis and the local neuronal population in auditory cortex (Aim 3). An experienced team of mentors and collaborators will provide training critical for the candidate's short- and long-term success, including: in vivo whole-cell recordings, genetic targeting of neuronal subtypes, optogenetic modulation of neural circuits, in vivo imaging of synaptic elements. The proposed training program combines hands-on training, formal mentorship, and consultation with experienced independent researchers, coursework, independent study, seminar attendance, and professional scientific meetings. In the long-term, this support will equip the candidate to lead a laboratory that merges cellular and systems approaches to explore the neural basis of flexible auditory perception.

描述（由申请人提供）：哺乳动物的听觉系统可以通过经验和行为环境进行修改，这是初级听觉皮层（A1）的一个重要特征，特别是在形成诸如语音、音乐和其他形式的感觉信号的表征方面。随着时间和经验的积累，动物可以了解到特定的声音而不是其他声音可以发出奖励信号。此外，动物还可以了解到，在不同的环境中，相同的声音需要不同的行为反应，例如，人类的声音。街上听到枪声与看电影时相比，PTSD 患者听到一声巨响可能会导致不同的行为反应，并且可能无法做出相同的区分，这种缺陷也与包括自闭症在内的发育和语言障碍有关。因此，对于正常或病理性听觉处理的研究至关重要。传统上，感觉信息被认为是以线性方式处理的，其中每个连续的大脑区域提取更复杂的特征，然后将其传输到赋予意义的高阶区域（前馈处理）。）。然而，在听觉皮层中，该模型越来越受到行为动物的神经记录的挑战，其中背景或行为状态在调节神经活动中发挥着重要作用，在相同的声音在一种背景（活跃背景）中引起注意但行为条件下会发生什么。在另一种情况下（被动环境）不需要注意？该提案中的初步数据表明，听觉皮层神经元在这两种情况下具有明显不同的活动模式，控制听觉皮层神经调节中心的这种环境依赖性活动的精确机制仍然未知。参与注意力可能会发挥鉴于其在长期可塑性和学习中的重要性，该提议将检验听觉皮层中的上下文依赖性是由于远程注意力信号直接作用于局部电路而产生的假设。进行测试的目的是测试两种情况下听觉皮层的突触输入（神经活动的组成部分）是否不同（目标 1）。其次，实验将测试来自基底核（大脑区域）的乙酰胆碱释放投射是否存在差异。第三，实验将通过观察来自大脑的注意力信号来测试在学习过程中上下文相关的活动是如何出现的。基底核和听觉皮层的局部神经元群（目标 3）经验丰富的导师和合作者团队将为候选人的短期和长期成功提供关键的培训，包括：体内全细胞记录、基因靶向。拟议的培训计划结合了实践培训、正式指导和经验丰富的独立研究人员的咨询、课程作业、独立研究、参加研讨会和专业科学会议。从长远来看，这种支持将使候选人能够领导一个融合细胞和系统方法的实验室，以探索灵活听觉感知的神经基础。