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

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

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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（由应用程序提供）：可以通过经验和行为上下文来修改哺乳动物的听觉系统。这是主要听觉皮层（A1）的重要特征，尤其是在形成语音，音乐和其他形式的声学通信等感觉信号的表示时。有了时间和经验，动物可以学习特定的声音，而其他人则可以发出信号。此外，动物还可以了解到，在不同情况下，相同的声音需要不同的行为反应。例如，在人类中，在街上听到的枪声而不是在电影中听到的声音可能会导致行为反应不同。相反，PTSD患者听到大声的爆炸声，可能无法进行相同的差异化。此类定义也在包括自闭症在内的发展和语言障碍中实施。因此，了解知觉灵活性的机制对于对正常或病理听觉处理的研究至关重要。通常，人们认为感官信息是以线性方式处理的，每个成功的大脑区域都提取更复杂的特征，然后将其传输到会议含义（馈送前进处理）的高阶区域。然而，在听觉皮层中，这种模型越来越受到行为动物的神经元记录的挑战，在这种动物中，情境或行为状态在调节神经元活动中起着重要作用。在行为条件下，同一声音在一个上下文（主动上下文）中引起注意的情况会发生什么，但不需要在另一个上下文（被动环境）中注意？该提案中的初步数据表明，在这两种情况下，听觉皮质神经元具有明显不同的活动模式。控制听觉皮层中这种依赖上下文活动的精确机制仍然未知。鉴于它们在长期可塑性和学习中的重要性，参与注意力的神经调节中心可能在上下文切换中起关键作用。该提案将检验以下假设：在听觉皮层中的上下文依赖性会出现，因为远程注意信号直接作用于本地电路。首先，将进行实验，以测试突触输入（神经元活动的基础）在两种情况下的听觉皮层中是否不同（AIM 1）。其次，实验将测试乙酰胆碱 - 从核Basalis（一个引起注意的大脑区域）中释放项目，在主动任务中是自然活跃的，并直接改变了听觉皮层的突触重量（AIM 2）。第三，实验将通过查看来自听觉皮层中的核心核和局部神经元种群的注意信号来测试在学习过程中如何出现上下文依赖性活动（AIM 3）。一支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至关重要的培训，包括：体内全细胞记录，神经元亚型的遗传靶向，神经元电路的光遗传学调节，突触元素的体内成像。拟议的培训计划结合了动手培训，正式的心态，并与经验丰富的独立研究人员，课程，独立研究，半明律出勤和专业科学会议结合了咨询。从长远来看，这种支持将使候选人能够领导一个合并细胞和系统方法以探索灵活听觉感知的神经基础的实验室。