Age-related and cell-type-specific changes in auditory cortical processing

老龄化是不可避免的。在与年龄相关的身体变化中，年龄相关性听力损失(ARHL)对我们来说是一个严重的问题。急性淋巴细胞性白血病是影响美国65岁及以上人群的三大最常见慢性健康疾病之一。在英国，近640万老年人患有某种形式的听力损失。据预测，这一数字还将进一步增加。事实上，世界卫生组织预测，到2030年，成人听力损失将成为英国十大疾病负担之一，仅次于糖尿病。虽然ARHL本身不会杀死我们，但它的影响是巨大的：ARHL显著降低了一个人与他人沟通的能力，导致对日常生活的重大影响。听力随年龄增长的另一个变化是听觉处理的缓慢。同样，这种与年龄相关的听觉处理迟缓导致日常交流困难。解决这些社会问题的一种方法是更好地理解老化的听觉系统。在这项建议中，我们将研究衰老如何影响听觉大脑中的听觉信息处理，特别是对人类语音理解至关重要的听觉皮质。在听觉皮质中有许多类型的神经元，但我们对这些不同的神经元之间如何相互通信以及神经元通信如何随年龄变化知之甚少。在这项提案中，我们将特别关注两个主要神经元组中的一个，称为抑制神经元，因为我们知道其他听觉脑区的抑制电路会受到老化的影响，但我们对老化的听觉皮质中的抑制电路知之甚少。我们将测试听觉皮质中的听觉处理随年龄变化的假设，这取决于细胞类型。为此，我们将结合动物模型中的先进技术。其中一项技术被称为大规模并行神经记录技术，它允许我们同时从100个神经元中读出活动。另一项技术被称为光遗传学，它允许我们以特定细胞类型的方式用光来控制神经元的活动。在这项建议中，我们特别致力于实现两个目标：第一，我们将表征衰老如何影响听觉皮质抑制神经元的信息处理。第二，通过用光激活抑制神经元，我们将评估衰老如何改变听觉皮质中抑制神经元的能力。我们的研究将为听觉处理中与年龄相关的变化机制提供进一步的见解，并为老化的听觉系统开发新的干预策略。

Ageing is unavoidable. Of age-related changes in our body, age-related hearing loss (ARHL) is a serious issue for us. ARHL is one of the top three most common chronic health conditions affecting individuals aged 65 years and older in the US. In the UK nearly 6.4 million elderly people suffer from some form of hearing loss. It is predicted that this number will increase further. Indeed the World Health Organisation predicts that by 2030 adult onset hearing loss will be in the top ten disease burdens in the UK, above diabetes. Although ARHL per se won't kill us, its impact is huge: ARHL significantly decreases the one's ability to communicate with others, resulting in a significant impact on daily life. Another change in hearing with age is the slowness of auditory processing. Again this age-related slowness in auditory processing leads difficulty in daily communication. One way to address these societal issues is a better understanding of the ageing auditory system.In this proposal we will investigate how ageing affects auditory information processing in the auditory brain, particularly the auditory cortex, which is essential for speech comprehension in humans. In the auditory cortex there are lots of types of neurons, but we know little about how such diverse neurons communicate with each other and how neuronal communications are changed with age. In this proposal we will particularly focus on one of two major neuron groups, called inhibitory neurons because we know that inhibitory circuits are affected by ageing in other auditory brain areas, but we know little about inhibitory circuits in the ageing auditory cortex.We will test the hypothesis that auditory processing in the auditory cortex is changed with age depending on cell-types.To this end, we will combine advanced technologies in animal models. One technology is called massively parallel neural recording technique, which allows us to readout activity from a hundred of neurons simultaneously. Another technology is called optogenetics, which allows us to control neuronal activity with light in a cell-type-specific manner. We are specifically aiming to achieve two goals in this proposal: firstly we will characterise how ageing affects information processing in inhibitory neurons of the auditory cortex.Secondly by activating inhibitory neurons with light we will assess how ageing can change abilities of inhibitory neurons in the auditory cortex.Our study will provide further insights into the mechanisms of age-related changes in auditory processing and the development of novel intervention strategies for the ageing auditory system.