早期知觉训练延缓大鼠听皮层调谐老龄化及其机制

Age-related hearing loss (presbycusis) affects not only the general hearing and auditory-related behaviors of older adults, but also their language and cognitive abilities. More recently, it has been proposed that age-related hearing loss is potentially associated with Alzheimer’s disease. While hearing aids can effectively compensate for the age-related elevation of hearing thresholds, they may not be able to overcome all hearing problems, particularly the degraded central auditory processing. It is thus important to investigate the neural bases underlying age-related hearing loss in the animal model, in order to treat this most common sensory deficit in the elderly. In this proposal, we will first examine the age-related changes in multi-parametric responses of auditory cortical neurons in levels of neural circuits and synapses by using rat as a research model. We will then assess the behavioral consequence of age-related hearing loss and subsequently examine the related cortical neural bases. To test the hypothesis that acoustic experiences in early life shape the auditory cortical processing in later life, we will finally examine the effects of early perceptual training on multi-parametric responses of cortical neurons in aged rats. These studies would bear great practical and theoretical importance for strategies of promoting degraded auditory cortical processing in the elderly through adulthood perceptual training.

老年性听觉障碍不仅影响老年人听觉及其相关行为，甚至影响言语乃至认知功能，并与老年性痴呆有潜在联系。虽然助听器可有效补偿老年性听觉障碍的外周功能(即听力阈值的提高)但却无法改善中枢听信息处理能力的衰退。因此，基于实验动物的年龄相关性听觉缺失中枢机制研究对深入了解老年性听觉障碍及其改善治疗极为重要。本项目以大鼠为听觉实验模型，首先研究听皮层神经元在神经网络及多模态水平调谐反应特性的老龄性变化及其突触分子机制，以期了解老年性听觉障碍的中枢机制；然后通过听知觉检测程序评估听觉老龄性变化的行为表征，并分析其与皮层听神经元多模态调谐特性变化的相关性，以探讨个体听觉行为表征老龄性变化的神经基础；最后，尝试在年轻大鼠通过知觉训练诱导听皮层靶向性的可塑性以延缓其多模态调谐特性的年龄相关性变化并考察其突触分子机制，为通过早期知觉训练诱导中枢听觉可塑性以延缓、改善老年性听觉功能退化的创新策略提供理论和实践依据。

老年性听觉障碍不仅影响老年人听觉及其相关行为，甚至影响言语乃至认知功能，并与老年性痴呆有潜在联系。虽然助听器可有效补偿老年性听觉障碍的外周功能（即听力阈值的提高）但却无法改善中枢听信息处理能力的衰退。因此，基于实验动物的年龄相关性听觉缺失中枢机制研究对深入了解老年性听觉障碍及其改善治疗极为重要。本项目以大鼠为听觉实验模型，研究听皮层神经元多模态调谐反应特性的老龄性变化及其知觉训练的影响效应。结果发现，老年动物的听觉分辨能力明显弱于年轻动物，这和老年动物听皮层神经元的多模态（包括频率、时相及方位）调谐反应特性退变有关；通过知觉训练诱导听皮层可塑性可在一定程度锐化其调谐反应特性的年龄相关性变化，且动物听觉相关行为也有一定改善，这些神经元反应及行为改变和训练诱导的听皮层抑制性中间神经元变化有关。我们的研究为通过知觉训练诱导听觉中枢可塑性以延缓、改善老龄性听觉功能退化的创新策略提供了理论依据。本项目已发表3篇研究论文（包括1篇PNAS和2篇Cerebral Cortex）。以这些成果为主，题为《大脑听觉皮层可塑性研究》的课题获得上海市自然科学奖三等奖（2019.1；排名第一）。