Pathological ensembles in the auditory thalamocortical circuit following acoustic trauma

声损伤后听觉丘脑皮层回路的病理整体

• 批准号: MR/J004448/1
• 负责人: Shuzo Sakata
• 金额: $ 28.49万
• 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: 2012
• 资助国家: 英国
• 起止时间: 2012 至 无数据
• 项目状态: 已结题
• 来源: https://gtr.ukri.org/projects?ref=MR%2FJ004448%2F1
• 关键词: Pathological; ensembles; auditory; thalamocortical; circuit

The brain is like a social network, where billions of neurons are connecting and chemically talking each other. In brain sciences, one of the biggest mysteries is how the brain can create sensations. While our sensations result from processing of sensory stimuli by the brain circuit, the brain circuit also creates abnormal sensations, such as a phantom limb, tinnitus and hallucinations, from which millions of people around the world is suffering. Tinnitus, for instance, is the perception of sound or noise in the absence of auditory stimuli. Many of us have some experience a buzzing or ringing in the ears, especially after exposure to loud noise, such as music or sports events. Although this is a temporary problem for most people, this phantom auditory perception is persistent in 5-15% of the general population. In around 2%, tinnitus causes severe impairment of the quality of lives, such as sleep disturbance, depression, anxiety, and even suicide. Moreover, tinnitus is strongly associated with ageing. Given the fact that human longevity is increasing, the impact of tinnitus on society will get worse. Therefore tinnitus is a major public health issue. But unfortunately treatment options remain limited.What is known about tinnitus? Over the past decades, scientists have identified several mechanisms of tinnitus in the brain. Although tinnitus is initiated by focal damage to the peripheral auditory pathway, so-called the cochlea, the central auditory pathway also struggles to adapt to it. For example, neurons in the central auditory pathway become hyperactive without auditory inputs. Tonal frequency maps in the brain, so-called tonotopic maps, are also altered. These abnormalities are thought as possible mechanisms of tinnitus. But we have not fully understood exactly how tinnitus is generated.There is an important brain circuit for sensory perception. This circuit consists of the thalamus and cortex. In the auditory system, they are called the auditory thalamus and auditory cortex, respectively. In general, the sensory thalamus is directly transferring sensory signals from periphery to the sensory cortex while the cortex is also returning signals back to the thalamus. This thalamocortical loop has long been implicated in sensory perceptions. Therefore we suspect that abnormal activity in the auditory thalamocortical circuit is a possible mechanism of phantom auditory perception, tinnitus. Although there is indirect evidence for this prediction, no one has directly measured neural activity from both the auditory thalamus and cortex in this context. In this proposed research, by using behavioural and state-of-the-art electrophysiological approaches, we aim to determine relationships between tinnitus and pathological activities in the auditory thalamus and cortex. The results of our research will provide further insights into the mechanisms of tinnitus at the level of neuronal circuits. Our long-term perspective envisions the development of better strategies to treat tinnitus. Therefore, this proposal will contribute to both sensory neuroscience and human health.

大脑就像一个社交网络，数十亿的神经元相互连接，并通过化学方式相互交谈。在脑科学中，最大的谜团之一是大脑如何创造感觉。虽然我们的感觉来自大脑回路对感官刺激的处理，但大脑回路也会产生异常感觉，如幻肢，耳鸣和幻觉，世界各地数百万人正在遭受这些感觉。例如，耳鸣是在没有听觉刺激的情况下对声音或噪音的感知。我们中的许多人都有过耳朵嗡嗡作响或耳鸣的经历，尤其是在暴露于音乐或体育赛事等巨响之后。虽然这对大多数人来说是一个暂时的问题，但这种幻听在5-15%的普通人群中是持续存在的。在大约2%的人中，耳鸣会严重损害生活质量，如睡眠障碍，抑郁，焦虑，甚至自杀。耳鸣与衰老密切相关。随着人类寿命的延长，耳鸣对社会的影响将越来越严重。耳鸣是一个严重的公共卫生问题。耳鸣的危害有哪些？耳鸣的危害有哪些？在过去的几十年里，科学家们已经确定了耳鸣在大脑中的几种机制。虽然耳鸣是由周围听觉通路（所谓的耳蜗）的局灶性损伤引起的，但中枢听觉通路也在努力适应它。例如，中枢听觉通路中的神经元在没有听觉输入的情况下变得过度活跃。大脑中的音调频率图，即所谓的音调分布图，也会发生改变。耳鸣的病因有哪些？耳鸣是一种常见的神经性疾病，它是由大脑中一个重要的神经回路控制的。这个回路由丘脑和皮层组成。在听觉系统中，它们分别被称为听觉丘脑和听觉皮层。一般来说，感觉丘脑直接将感觉信号从外周传递到感觉皮层，而皮层也将信号返回到丘脑。这种丘脑皮层回路长期以来与感觉知觉有关。因此，我们怀疑听觉丘脑皮层回路的异常活动可能是幻听耳鸣的一个机制。虽然有间接证据支持这一预测，但没有人直接测量过听觉丘脑和皮层的神经活动。在这项拟议的研究中，通过使用行为和最先进的电生理方法，我们的目标是确定耳鸣和听觉丘脑和皮层的病理活动之间的关系。我们的研究结果将在神经元回路水平上提供对耳鸣机制的进一步见解。我们的长期观点设想更好的策略来治疗耳鸣的发展。因此，这一建议将有助于感觉神经科学和人类健康。

项目成果

Optogenetic activation of neocortical neurons in vivo with a sapphire-based micro-scale LED probe.

• DOI: 10.3389/fncir.2015.00025
• 发表时间: 2015
• 期刊: Frontiers in neural circuits
• 影响因子: 3.5
• 作者: McAlinden N;Gu E;Dawson MD;Sakata S;Mathieson K
• 通讯作者: Mathieson K

Laminar-dependent effects of cortical state on auditory cortical spontaneous activity.

• DOI: 10.3389/fncir.2012.00109
• 发表时间: 2012
• 期刊: Frontiers in neural circuits
• 影响因子: 3.5
• 作者: Sakata S;Harris KD
• 通讯作者: Harris KD

State-dependent and cell type-specific temporal processing in auditory thalamocortical circuit.

• DOI: 10.1038/srep18873
• 发表时间: 2016-01-05
• 期刊: Scientific reports
• 影响因子: 4.6
• 作者: Sakata S