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

听觉皮层处理中与年龄相关和细胞类型特异性的变化

• 批准号: BB/M00905X/1
• 负责人: Shuzo Sakata
• 金额: $ 45.83万
• 依托单位: University of Strathclyde
• 依托单位国家: 英国
• 项目类别: Research Grant
• 财政年份: 2015
• 资助国家: 英国
• 起止时间: 2015 至 无数据
• 项目状态: 已结题
• 来源: https://gtr.ukri.org/projects?ref=BB%2FM00905X%2F1
• 关键词: Age; related; cell; type; specific

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.

衰老是不可避免的。在我们身体与年龄相关的变化中，年龄相关性听力损失（ARHL）对我们来说是一个严重的问题。ARHL是影响美国65岁及以上人群的三大最常见慢性健康状况之一。在英国，大约有640万老年人患有某种形式的听力损失。据预测，这一数字将进一步增加。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，超过糖尿病。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，从而对日常生活产生重大影响。随着年龄的增长，听力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缓慢导致日常交流困难。解决这些社会问题的方法之一是更好地了解衰老的听觉系统。在本研究中，我们将研究衰老如何影响听觉大脑中的听觉信息处理，特别是听觉皮层，这对人类的语音理解至关重要。在听觉皮层中，有许多类型的神经元，但我们对这些不同的神经元如何相互交流以及神经元的交流如何随年龄而变化知之甚少。在这个建议中，我们将特别关注两个主要神经元群之一，称为抑制神经元，因为我们知道抑制回路受到其他听觉大脑区域老化的影响，但我们对老化听觉皮层中的抑制回路知之甚少。我们将测试听觉皮层中的听觉处理随年龄变化取决于细胞类型的假设。为此，我们将在动物模型中结合联合收割机的先进技术。一项技术被称为大规模并行神经记录技术，它允许我们同时读出一百个神经元的活动。另一种技术被称为光遗传学，它允许我们以细胞类型特异性的方式用光来控制神经元的活动。我们在这一建议中具体旨在实现两个目标：首先，我们将研究年龄对听觉皮层抑制性神经元信息加工的影响，其次，通过光激活抑制性神经元，我们将研究年龄对听觉皮层抑制性神经元信息加工能力的影响，我们的研究将为进一步了解年龄对听觉皮层抑制性神经元信息加工能力的影响提供理论依据。听觉处理的相关变化以及针对老龄化听觉系统的新干预策略的发展。

项目成果

Disentangling neuronal inhibition and inhibitory pathways in the lateral habenula

解开外侧缰核的神经元抑制和抑制通路

• DOI: 10.1101/633271
• 发表时间: 2019
• 作者: Webster J

State-dependent pontine ensemble dynamics and interactions with cortex across sleep states

• DOI: 10.1101/752683
• 发表时间: 2019-09
• 期刊: bioRxiv
• 作者: Tomomi Tsunematsu;Amisha A. Patel;A. Onken;S. Sakata

Pathway-dependent regulation of sleep dynamics in a network model of the sleep-wake cycle

睡眠-觉醒周期网络模型中睡眠动态的通路依赖性调节

• DOI: 10.1101/705822
• 发表时间: 2019
• 作者: Héricé C

Circuit mechanisms and computational models of REM sleep.

• DOI: 10.1016/j.neures.2018.08.003
• 发表时间: 2019-03
• 期刊: Neuroscience research
• 影响因子: 2.9
• 作者: Héricé C;Patel AA;Sakata S
• 通讯作者: Sakata S

Cre-Dependent Optogenetic Transgenic Mice Without Early Age-Related Hearing Loss

• DOI: 10.1101/416164
• 发表时间: 2018-09
• 期刊: Frontiers in Aging Neuroscience
• 影响因子: 4.8
• 作者: D. Lyngholm;S. Sakata