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: 10028097
• 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/10028097
• 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; 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; outcome forecast; 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.

项目摘要 有充分的证据表明，成年人大脑的可塑性有限。在……里面 具体地说，依赖感觉经验的皮质回路的可塑性在 发展，被称为关键时期。因此，感觉加工的恢复和精炼在 成年人。例如，人工耳蜗植入患者的语音识别成功率为 相当低，如果手术是在生命的后期进行的。因此发现了可以恢复成人大脑皮质的机制 可塑性对于听力的恢复或在发生时治疗异常的听觉处理是必不可少的。 耳鸣。我们发现，暂时的视觉剥夺在产生大规模可塑性方面是相当有效的 成年小鼠的初级听觉皮质(A1)。这种变化发生在前馈兴奋增强 从初级听觉丘脑(MGBv)到第四层(L4)以及L4到L2/3的突触。这是 伴有外侧皮质来源的突触变弱至A1的L2/3。同时，我们 还观察到A1、L4和L2/3的皮质环路的细化。总的来说，这些变化表明A1 电路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 视功能中A1、L4神经元感受野细化及检测阈值降低的观察 剥夺了小鼠的权利。在这项应用中，我们的目标是确定参与驱动成人A1可塑性的机制 视觉剥夺，以及视觉剥夺是否改善了成年人的听觉行为。基于我们的 观察视觉剥夺诱导丘脑皮质(TC)对A1、L4传入的增强需要 试听，但没有由于听觉环境的变化，我们推测在中枢适应 通过丘脑和大脑皮层传递听觉信号的回路。特别是，我们假设 短期视觉剥夺通过调节抑制回路水平促进成人A1的可塑性 丘脑和皮质(目标1)。伴视力减退后A1区的回路和突触适应 精炼A1 L4神经功能，预计将增强听觉功能。我们将研究如何缩短- 视觉剥夺改变了成年人的听觉行为任务，并调查这是否归因于 在活体双光子听觉任务中A1神经元反应和群体编码的变化 成像(目标2)。我们提议的研究结果将提供对如何短期内 视觉剥夺通过调节丘脑和皮质回路使成人A1的可塑性增强，并将提供 增强成人大脑中的听觉处理的手段，这可能有助于治疗方案的发展 用于增强或恢复人工耳蜗术后更好的预后所需的听觉功能 植入物。此外，我们的结果可以推广到大脑皮层回路如何适应 失去主要的输入，因为它可能发生在损伤、中风和神经元退化期间。