Pathological ensembles in the auditory thalamocortical circuit following acoustic trauma

大脑就像一个社交网络，数十亿的神经元连接在一起，通过化学方式相互交流。在脑科学中，最大的谜团之一是大脑如何产生感觉。虽然我们的感觉来自于大脑回路对感官刺激的处理，但大脑回路也会产生异常的感觉，比如幻肢、耳鸣和幻觉，这些都是世界上数百万人正在遭受的痛苦。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鸣的经历，尤其是在听了音乐或体育赛事等噪音之后。虽然这对大多数人来说是暂时的问题，但在一般人群中有5-15%的人会持续存在这种幻听。在大约2%的患者中，耳鸣会对生活质量造成严重损害，如睡眠障碍、抑郁、焦虑，甚至自杀。此外，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大。因此，耳鸣是一个重大的公共卫生问题。但不幸的是，治疗选择仍然有限。关于耳鸣我们知道些什么？在过去的几十年里，科学家们已经确定了大脑中耳鸣的几种机制。虽然耳鸣是由周围听觉通路（即耳蜗）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，即所谓的张力图，也会发生改变。这些异常被认为是耳鸣的可能机制。但我们还没有完全了解耳鸣是如何产生的。大脑中有一个重要的感官知觉回路。这个回路由丘脑和大脑皮层组成。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。这种丘脑皮质环长期以来一直与感官知觉有关。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机制之一。尽管有间接证据支持这一预测，但在这种情况下，还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学方法，我们旨在确定耳鸣与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为耳鸣的机制提供进一步的见解。我们的长期愿景是开发更好的治疗耳鸣的策略。因此，这一建议将有助于感觉神经科学和人类健康。

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.