Pathological ensembles in the auditory thalamocortical circuit following acoustic trauma

点击翻译按钮获取中文摘要

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.