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: 10748930
• 负责人: PATRICK O KANOLD
• 金额: $ 1.88万
• 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/10748930
• 关键词: Adult; Auditory; Auditory area; Automobile Driving; Behavior; Behavioral; Blindness; Brain; Chemosensitization; Cochlear Implants; Detection; Development; Environment; Excitatory Synapse; Hearing; Image; Injury; Lateral; Life; Mediating; Modality; Mus; Nerve Degeneration; Neurons; Neurophysiology - biologic function; Operative Surgical Procedures; Patients; Performance; Population; Prognosis; Publishing; Recovery; Regulation; Sensory; Signal Transduction; Source; Stroke; Synapses; Thalamic structure; Therapeutic; Time; Tinnitus; Vision; Visual; auditory processing; auditory thalamus; critical period; experience; improved; in vivo; insight; receptive field; response; speech recognition; success; therapy development; two-photon; visual deprivation

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.

项目摘要 有充分的文献证明，大脑经历可塑性的能力在成年人中受到限制。在 特别的，感官体验依赖性皮层电路的可塑性仅限于有限的时间 开发，称为关键时期。因此，很难在感官处理中恢复和完善 成年人。例如，人工耳蜗植入物患者的语音识别成功率变成 如果手术在以后的生活中进行，则很低。因此发现可以恢复成人皮质的机制 可塑性至关重 带有耳鸣。我们发现，临时视觉剥夺在产生大规模可塑性方面非常有效 小鼠的成年初级听觉皮层（A1）。这样的变化发生在进餐兴奋性的增强 从主要听觉丘脑（MGBV）到第4（L4）以及L4至L2/3的突触。这是 伴随着从侧面内部源到A1的L2/3引起的突触削弱。并行，我们 还观察到A1 L4和L2/3的皮质回路的细化。总的来说，这些变化表明A1 电路适应以更好地处理自下而上的听觉输入，这与我们已发布的 观察A1 L4神经元接受场的细化和视觉阈值的降低 被剥夺的老鼠。在此应用中，我们旨在确定驾驶成人A1可塑性涉及的机制 视觉剥夺以及视觉剥夺是否可以改善成人的听觉行为。基于我们 观察到视觉剥夺引起丘脑皮质（TC）输入到A1 L4的增强 试镜，但由于听觉环境的变化没有，我们推测 电路介导了通过丘脑和皮质的听觉信号。特别是，我们假设 短期视觉剥夺通过调节抑制回路的水平来促进成人的A1可塑性 丘脑和皮层（目标1）。伴随视力丧失后在A1中看到的电路和突触适应 A1 L4神经功能的细化，预计可以增强听觉功能。我们将研究如何短暂 术语视觉剥夺会改变成人的听觉行为任务，并调查是否归因于 使用Vivo 2-Photon在听觉任务过程中A1神经元反应和人群编码的变化 成像（目标2）。我们拟议的研究的结果将提供有关短期如何的机械理解 视觉剥夺可以通过调节丘脑和皮质电路来使成人A1的可塑性，并将提供 增强成人大脑中的听觉处理的手段，可以使治疗选择的发展有益 为了增强或恢复听觉功能，需要更好地预测人工耳蜗 植入物。此外，我们的结果可以概括以提供有关皮质电路如何适应的见解 在受伤，中风和神经元变性过程中可能会失去重大输入。