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定位附近的声音，这有助于生存。在听觉系统中，声源的位置是从双耳和单耳线索中集中导出的。在单侧听力损失的情况下，双耳线索不可用，限制了空间听力，这损害了语音处理和整体听力能力。然而，单耳闭塞的人类和动物可以重新获得灵敏度的声音定位时，双耳线索是缺席。它是假设的声音定位的可观察到的再学习依赖于上下文相关的重新校准的听觉空间的单声道线索。因此，中央听觉可塑性机制必须存在重新加权双耳和单耳线索在任务参与。下丘（IC）的外壳可能是这种空间可塑性的主要部位。当从初级听觉皮层，直接接触壳IC沉默下降的预测，动物无法重新学习声音定位，表明壳IC在空间可塑性的强大作用。然而，哺乳动物壳IC中空间的生理表征和对改变的输入的适应机制知之甚少。弥合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定位。本研究的主要目的是探讨听觉空间在壳IC中的表征，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，我们将在头部固定的小鼠中使用双光子Ca2+成像和行为测定的组合。这种尖端技术能够在数周的时间内监测壳IC中相同神经元的活动，以评估随时间的可塑性。我们将在被动听实验中对听力正常和单侧听力受损小鼠的壳IC中的听觉空间表征进行系统的研究。在下一步中，我们将测试学习如何驱动单耳听力损失后壳IC中听觉空间表征的重组。将训练小鼠在成像期间区分来自左半野和右半野的声音呈现。动物将接受单侧耳塞以研究壳IC中的空间调谐的动力学，同时小鼠重新学习定位声音。最后一个实验将使用相同的行为方法，但重点是皮层输入到外壳IC。在使用轴突Ca2+成像重新学习声音定位期间，将在壳IC中可视化皮质丘投影。我们的研究结果将进一步确立壳IC在空间听觉中的作用，并加深我们对成人感觉可塑性生理学和双耳听觉的理解。

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.