Auditory space representation and its plasticity in the shell of the inferior colliculus

空间听觉使人类和动物能够将附近的声音局部化，这有助于生存。在听觉系统中，声源的位置主要来自双耳和单耳提示。在单侧听力损失的情况下，双耳提示不可用，从而限制了空间听力，从而损害了言语处理和整体听力能力。然而，在没有双耳提示的情况下，单耳闭塞的人类和动物可以在声音定位中重新获得敏感性。假设可观察到的声音局部化的重新学习依赖于单声道线索对听觉空间的上下文依赖的重新校准。因此，中枢听觉可塑性机制必须存在，以在任务参与过程中对双耳和单耳线索进行重新加权。下丘(IC)的壳可能是这种空间可塑性的主要部位。当抑制直接接触外壳IC的初级听觉皮质的下行投射时，动物无法重新学习声音定位，这表明外壳IC在空间可塑性中发挥着强大的作用。然而，哺乳动物外壳IC中空间的生理表征以及适应改变输入的机制还知之甚少。缩小这一知识差距将提高我们对学习练习如何支持可塑性过程的理解，以及如何将其作为一种简单的方法来改善单耳听力损失后的声音局部化。该项目的主要目的是研究听觉空间在外壳IC中的表现，并揭示行为动物单耳听力损失后中枢听觉可塑性的机制。为此，我们将使用双光子钙成像和头部固定小鼠的行为分析相结合的方法。这项尖端技术可以在几周的时间内监测贝壳IC中相同神经元的活动，以评估随时间推移的可塑性。在被动听音实验中，我们将对听力正常小鼠和单侧听力受损小鼠的壳层IC的听觉空间表征进行系统的研究。在下一步，我们将测试学习如何驱动单耳听力损失后贝壳IC中听觉空间表征的重新组织。小鼠将被训练在成像过程中辨别来自左半脑和右半脑的声音。动物将接受单侧耳塞，以研究贝壳IC中的空间调谐动力学，而小鼠则重新学习声音的本地化。最后一个实验将使用相同的行为方法，但重点是贝壳IC的大脑皮层输入。在使用轴突钙离子成像重新学习声音定位的过程中，皮质-丘脑投射将在外壳IC中可视化。我们的结果将进一步确定贝壳IC在空间听力中的作用，并加深我们对成年感觉可塑性生理学和一般双耳听力的理解。

Spatial hearing enables humans and animals to localise sounds in their vicinity which contributes to survival. In the auditory system, locations of sound sources are derived centrally from binaural and monaural cues. In the case of unilateral hearing loss, binaural cues are not available, limiting spatial hearing which impairs speech processing and overall hearing ability. However, monaurally occluded humans and animals can regain sensitivity in sound localisation when binaural cues are absent. It is assumed that the observable re-learning of sound localisation relies on the context-dependent re-calibration of auditory space by monaural cues. Thus, central auditory plasticity mechanisms must exist to re-weight binaural and monaural cues during task engagement. The shell of the inferior colliculus (IC) may act as a dominant site for this spatial plasticity. When silencing descending projections from the primary auditory cortex, which directly contact shell IC, animals are unable to re-learn sound localisation, indicating the strong role of shell IC in spatial plasticity. However, the physiological representation of space in the mammalian shell IC and the mechanisms of adaptation to altered input are poorly understood. Closing this gap in knowledge would improve our understanding of how learning exercises might support plasticity processes and how they could be applied as a simple approach to improve sound localisation following monaural hearing loss. The major objectives of this project are to investigate the representation of auditory space in the shell IC and to reveal mechanisms of central auditory plasticity following monaural hearing loss in the behaving animal. To this end, we will use a combination of 2-photon Ca2+-imaging and behavioural assays in head-fixed mice. This cutting-edge technique enables monitoring activity of the same neurons in the shell IC over a duration of weeks to assess plasticity of over time. We will perform a systematic investigation of auditory space representation in the shell IC of normal hearing vs. unilaterally hearing-impaired mice in passive listening experiments. In the next step, we will test how learning drives the re-organisation of auditory space representation in the shell IC following monaural hearing loss. Mice will be trained to discriminate between sound presentations from the left and the right hemifield during imaging. Animals will receive a unilateral earplug to investigate dynamics of spatial tuning in the shell IC while mice re-learn to localise sounds. The last experiment will use the same behavioural approach but with a focus on cortical input into the shell IC. Cortico-collicular projections will be visualised in the shell IC during re-learning of sound localisation using axonal Ca2+-imaging. Our results will further establish the role of the shell IC in spatial hearing and deepen our understanding about the physiology of sensory plasticity in adulthood and binaural hearing in general.