Cross-modal enhancement of auditory plasticity and performance in adults

跨模式增强成人听觉可塑性和表现

• 批准号: 10203918
• 负责人: PATRICK O KANOLD
• 金额: $ 49.17万
• 依托单位: JOHNS HOPKINS UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2020
• 资助国家: 美国
• 起止时间: 2020-07-01 至 2025-06-30
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10203918
• 关键词: Adult; Affect; Area; Auditory; Auditory area; Automobile Driving; Behavior; Behavioral; Blindness; Brain; Cell Nucleus; Cells; Chemosensitization; Cochlear Implants; Data; Detection; Development; Discrimination; Disinhibition; Environment; Excitatory Synapse; Feedback; Hearing; Image; Injury; Lateral; Life; Mediating; Modality; Mus; Nerve Degeneration; Neurons; Neurophysiology - biologic function; Operative Surgical Procedures; Organ; Patients; Performance; Peripheral; Population; Prognosis; Publishing; Recovery; Recovery of Function; Regulation; Reporting; Research; Rogaine; Role; Sensory; Signal Transduction; Source; Stimulus; Stroke; Synapses; Testing; Thalamic structure; Therapeutic; Time; Tinnitus; Vision; Visually Impaired Persons; Work; auditory processing; auditory thalamus; base; behavioral outcome; critical period; experience; improved; in vivo; information processing; insight; novel; postnatal development; receptive field; response; sound; speech recognition; success; therapy development; two-photon; visual deprivation; vocalization

Project Summary It is well documented that the ability of the brain to undergo plasticity becomes limited in adults. In particular, sensory experience-dependent plasticity of cortical circuits is rather confined to a limited time during development, termed the critical period. Recovery and refinement of sensory processing is therefore difficult in adults. For example, the success rate of speech recognition in artificial cochlear implant patients becomes quite low, if the surgery is done later in life. Hence discovery of mechanisms that can recover adult cortical plasticity is of essence to benefit recovery of hearing or for treating abnormal auditory processing as occurs with tinnitus. We found that temporary visual deprivation is quite effective at producing large-scale plasticity in the adult primary auditory cortex (A1) of mice. Such changes occurred as potentiation of feedforward excitatory synapses from the primary auditory thalamus (MGBv) to layer 4 (L4) as well as L4 to L2/3. This was accompanied by weakening of synapses arising from lateral intracortical sources to L2/3 of A1. In parallel, we also observed refinement of cortical circuits of A1 L4 and L2/3. Collectively, these changes suggest that A1 circuit adapts to allow better processing of bottom-up auditory inputs, which is consistent with our published observation of refinement of A1 L4 neuronal receptive field and lowering of detection threshold in visually deprived mice. In this application, we aim to determine the mechanisms involved in driving adult A1 plasticity with visual deprivation, and whether visual deprivation improves auditory behavior in adults. Based on our observation that visual deprivation induced potentiation of thalamocortical (TC) inputs to A1 L4 requires audition, but no due to changes in the auditory environment, we surmise that there is central adaptation in circuits mediating auditory signals going through the thalamus and the cortex. In particular, we hypothesize that short-term visual deprivation promotes A1 plasticity in adults by regulating inhibitory circuits at the level of thalamus and cortex (Aim 1). The circuit and synaptic adaptation seen in A1 following vision loss accompanied refinement of A1 L4 neural function, and is predicted to enhance auditory function. We will examine how short- term visual deprivation alters auditory behavioral tasks in adults, and investigate whether this is due to changes in A1 neuronal responses and population encoding during auditory tasks using in vivo 2-photon imaging (Aim 2). Results from our proposed study will provide mechanistic understanding on how short-term visual deprivation enables plasticity of adult A1 via regulation of thalamic and cortical circuits, and will provide means to enhance auditory processing in the adult brain that could benefit development of treatment options for enhancing or recovering auditory function as would be needed for better prognosis of artificial cochlear implants. Furthermore, our results can be generalized to provide insights into how cortical circuits adapt to losing major inputs as it may happen during injury, stroke, and neuronal degeneration.

项目概要 有充分证据表明，成年人大脑的可塑性能力受到限制。在 特别是，皮层回路的感觉经验依赖性可塑性相当局限于在有限的时间内 发展的关键时期。因此，感觉处理的恢复和完善是很困难的。 成年人。例如，人工耳蜗植入患者的语音识别成功率变为 如果手术是在晚年进行的话，则相当低。因此发现了可以恢复成人皮质的机制 可塑性对于有利于听力恢复或治疗出现的异常听觉处理至关重要 伴有耳鸣。我们发现暂时的视觉剥夺对于产生大规模的可塑性非常有效 成年小鼠的初级听觉皮层（A1）。这种变化是随着前馈兴奋性的增强而发生的。 从初级听觉丘脑 (MGBv) 到第 4 层 (L4) 以及 L4 到 L2/3 的突触。这是 伴随着从外侧皮质内源到 A1 的 L2/3 产生的突触减弱。与此同时，我们 还观察到 A1 L4 和 L2/3 皮质回路的细化。总的来说，这些变化表明 A1 电路进行调整以允许更好地处理自下而上的听觉输入，这与我们发布的一致 观察 A1 L4 神经元感受野的细化和视觉检测阈值的降低 被剥夺的老鼠。在此应用中，我们的目标是确定驱动成人 A1 可塑性的机制 视觉剥夺，以及视觉剥夺是否会改善成年人的听觉行为。基于我们的 观察到视觉剥夺诱导丘脑皮质 (TC) 输入 A1 L4 的增强需要 试听，但由于听觉环境的变化而没有，我们推测存在中枢适应 介导穿过丘脑和皮层的听觉信号的电路。特别地，我们假设 短期视觉剥夺通过调节 A1 水平的抑制回路来促进成人 A1 可塑性 丘脑和皮质（目标 1）。视力丧失后 A1 中看到的电路和突触适应 改善 A1 L4 神经功能，预计可增强听觉功能。我们将研究如何短- 视觉剥夺会改变成年人的听觉行为任务，并调查这是否是由于 使用体内 2 光子进行听觉任务期间 A1 神经元反应和群体编码的变化 成像（目标 2）。我们提出的研究结果将为短期如何 视觉剥夺通过丘脑和皮质回路的调节使成人 A1 具有可塑性，并将提供 增强成人大脑听觉处理的手段，这可能有利于治疗方案的开发 用于增强或恢复听觉功能，这是人工耳蜗更好预后所需的 植入物。此外，我们的结果可以推广，以深入了解皮层回路如何适应 失去主要输入，因为在受伤、中风和神经元变性期间可能会发生这种情况。