Synaptic basis of perceptual learning in primary auditory cortex

初级听觉皮层知觉学习的突触基础

• 批准号: 10055734
• 负责人: Robert Crooks Froemke
• 金额: $ 38.73万
• 依托单位: NEW YORK UNIVERSITY SCHOOL OF MEDICINE
• 依托单位国家: 美国
• 财政年份: 2012
• 资助国家: 美国
• 起止时间: 2012-12-02 至 2022-11-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10055734
• 关键词: Acetylcholine; Adult; Affect; Animals; Area; Arousal; Auditory; Auditory Perception; Auditory area; Auditory system; Axon; Basal Nucleus of Meynert; Behavior; Behavioral; Brain; Cells; Cochlear Implants; Coupled; Cues; Data; Detection; Devices; Disease; Goals; Head; Hearing; Hearing Aids; Hour; Image; Imaging Techniques; Impairment; Individual; Language Development; Language Disorders; Learning; Link; Measurement; Measures; Medical Device Designs; Memory; Modeling; Modification; Monitor; Motivation; Mus; Music; Neuromodulator; Neuronal Plasticity; Neurons; Norepinephrine; Output; Pathologic; Perception; Perceptual learning; Performance; Pharmacology; Phase; Physiological; Population; Procedures; Prosthesis Design; Rattus; Recovery; Rewards; Rodent; Sensory; Series; Signal Transduction; Speech; Stimulus; Synapses; Synaptic plasticity; System; Task Performances; Testing; Therapeutic; Time; Training; Training Programs; Whole-Cell Recordings; Work; awake; behavioral response; cholinergic; cholinergic neuron; cost; deafness; excitatory neuron; experience; experimental study; hearing impairment; hearing restoration; imaging modality; improved; improved outcome; in vivo; information processing; inhibitory neuron; language impairment; locus ceruleus structure; neural circuit; neuroregulation; noradrenergic; novel strategies; optogenetics; recruit; relating to nervous system; response; selective attention; sound; speech processing; treatment strategy; two-photon

Project Summary The brain has the remarkable capability to change in response to experience. This plasticity is essential for learning and memory, and is an important feature of the auditory cortex, especially for learning the significance of sensory signals such as speech, for the use of devices such as cochlear implants, and for recovery after short- term deafness. These changes are thought to occur primarily at synapses, basic units of information processing and plasticity. Long-term synaptic plasticity requires sensory experience and activation of neuromodulatory systems which convey behavioral context to local cortical circuits. However, little is known about the interactions between synaptic inputs and release of neuromodulators in vivo, making it challenging to relate perceptual learning to plasticity in the auditory cortex or other brain areas. Recently we developed an approach to measuring dynamics of synaptic modifications for hours, coupled with imaging techniques enabling us to monitor the same cells over days during training, directly monitoring and manipulating activity in behaving mice. These approaches allow for a close examination of links between modulation, cortical plasticity and auditory perceptual learning. Specifically, we will study how auditory perceptual training activates the cholinergic vs noradrenergic modulatory systems. These two modulators are principally involved in selective attention towards behaviorally- important stimuli, general arousal, and learning. However, there may be important functional differences in these systems in terms of when they are active during different phases of training or consequences of cholinergic and noradrenergic modulation on auditory neurons for contextual information processing. This proposal describes a series of imaging, recording, optogenetic, and behavioral experiments that will compare and contrast the effects of locus coeruleus activation and norepinephrine release vs the effects of nucleus basalis activation and cholinergic modulation on the primary auditory cortex of behaving mice. Many studies have highlighted the importance of recording in awake animals during behavior, and we will first examine how ensembles of excitatory and inhibitory neurons are affected by learning over the entire duration of training, as animals go from naïve and poor performers, to having reliable performance on an auditory detection and recognition task we have used in the lab for years. Next, we determine when and how cholinergic and noradrenergic modulation affect behavioral and neural responses. Finally, we will make some of the first direct measurements of modulatory neuron responses, asking how these systems are activated by task-relevant variables such as sounds linked to reward. In summary, here we use in vivo recording and imaging methods to ask how behavioral training engages and modifies noradrenergic and cholinergic systems, to collectively affect auditory cortical processing and persistently improve auditory perceptual abilities in behaving mice.

项目概要 大脑具有根据经验做出改变的非凡能力。这种可塑性对于 学习和记忆，是听觉皮层的重要特征，尤其对于学习的意义 诸如语音等感觉信号，用于人工耳蜗等设备的使用，以及短暂恢复后的恢复 术语耳聋。这些变化被认为主要发生在突触，信息处理的基本单位 和可塑性。长期突触可塑性需要感觉体验和神经调节的激活 将行为背景传递给局部皮层回路的系统。然而，人们对相互作用知之甚少 体内突触输入和神经调节剂释放之间的关系，使得将知觉联系起来具有挑战性 学习听觉皮层或其他大脑区域的可塑性。最近我们开发了一种测量方法 数小时内突触修饰的动态，再加上成像技术使我们能够监测相同的情况 在训练期间连续几天观察细胞，直接监测和操纵行为小鼠的活动。这些方法 允许仔细检查调制、皮质可塑性和听觉感知学习之间的联系。 具体来说，我们将研究听觉感知训练如何激活胆碱能与去甲肾上腺素能 调节系统。这两个调节器主要涉及对行为的选择性注意 重要的刺激、一般的唤醒和学习。然而，这些可能存在重要的功能差异 系统在训练的不同阶段何时活跃或胆碱能和的后果 对听觉神经元进行去甲肾上腺素能调节，以进行上下文信息处理。该提案描述了一个 一系列成像、记录、光遗传学和行为实验将比较和对比效果 蓝斑激活和去甲肾上腺素释放与基底核激活和去甲肾上腺素释放的影响 对行为小鼠初级听觉皮层的胆碱能调节。许多研究都强调 记录清醒动物行为过程的重要性，我们将首先研究兴奋性的集合如何 抑制性神经元在整个训练过程中都会受到学习的影响，因为动物从天真到 表现不佳的人，在我们使用的听觉检测和识别任务中具有可靠的表现 实验室多年。接下来，我们确定胆碱能和去甲肾上腺素能调节何时以及如何影响行为 和神经反应。最后，我们将对调节神经元进行一些首次直接测量 响应，询问这些系统如何被任务相关变量（例如与奖励相关的声音）激活。 综上所述，我们在这里使用体内记录和成像方法来询问行为训练如何进行 并修改去甲肾上腺素能和胆碱能系统，共同影响听觉皮层处理和 持续改善行为小鼠的听觉感知能力。