Cross-modal enhancement of auditory plasticity and performance in adults

项目摘要 有充分的证据表明，成年人的大脑可塑性受到限制。在 特别是，皮层回路的感觉经验依赖性可塑性相当局限于有限的时间， 发展，称为关键时期。因此，感官加工的恢复和改进是困难的， 成年人了例如，人工耳蜗植入患者的语音识别成功率成为 如果手术是在以后的生活中进行的话，会非常低。因此发现了可以恢复成年人大脑皮层的机制 可塑性对于听力的恢复或治疗异常的听觉处理是至关重要的 耳鸣我们发现，暂时的视觉剥夺在产生大规模的可塑性方面非常有效， 成年小鼠的初级听觉皮层（A1）。这种变化发生在前馈兴奋性增强 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的突触的减弱。同时，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 电路适应允许更好地处理自下而上的听觉输入，这与我们发表的 视觉上观察到A1 L4神经元感受野的细化和检测阈值的降低 被剥夺的老鼠在这个应用中，我们的目标是确定参与驱动成人A1可塑性的机制 以及视觉剥夺是否能改善成年人的听觉行为。基于我们 视觉剥夺诱导的丘脑皮层（TC）对A1 L4的输入增强需要 听觉，但没有由于听觉环境的变化，我们推测，有中枢适应， 通过丘脑和皮层传递听觉信号的回路。特别是，我们假设 短期的视觉剥夺通过调节抑制回路，促进成年人的A1可塑性。 丘脑和皮质（Aim 1）。在视力丧失后的A1中观察到的回路和突触适应， A1 L4神经功能的细化，并预测增强听觉功能。我们将研究如何短- 长期视觉剥夺改变了成年人的听觉行为任务，并调查这是否是由于 在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（Aim 2）。从我们提出的研究结果将提供机械的理解如何短期 视觉剥夺通过调节丘脑和皮层回路使成人A1可塑性，并将提供 增强成人大脑听觉处理的方法，这可能有助于开发治疗方案 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到提供洞察皮层电路如何适应 在损伤、中风和神经元变性期间可能发生的主要输入丢失。

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.