Auditory processing by distributed circuits in the new vertebrate model Danionella translucida

为了确保动物的生存，分布式神经元网络执行复杂的计算来检测和辨别环境刺激的本质。为了研究这些计算的神经基础，我们需要观察跨越多个大脑区域的许多神经元的活动。然而，方法上的限制导致了对单个细胞或孤立大脑区域的小群神经元的关注。对大脑各区域神经元群体活动的密集记录不仅可以揭示单细胞记录所遗漏的罕见细胞和反应类型，还可以研究群体水平的表征、拓扑结构和区域间的相互作用。提出的项目的目标是了解声音信息是如何通过脊椎动物听觉通路的连续处理步骤的神经元群转换的。为了实现这一目标，我们将利用透明发声鱼的独特特性，使我们能够首次密集测量成年脊椎动物整个听觉系统的神经元群活动。我们的目标是利用神经示踪剂、组织清除和全脑成像的靶向应用来绘制丹尼欧菌的听觉解剖图谱。然后，这将作为全脑功能双光子成像的基础，通过听觉通路对感觉诱发的神经元群活动进行成像。最后，我们将结合功能成像和追踪来识别和监测投射神经元及其下游目标脑区的活动。如果成功，该研究将使丹尼ella成为第一个具有完整听觉处理链的成年脊椎动物模式生物，并将在种群水平上为脊椎动物听觉通路的结构和功能提供重要的见解。

To ensure an animal’s survival, distributed networks of neurons perform intricate computations to detect and discern the nature of environmental stimuli. In order to study the neural basis of these computations we need to observe the activity of many neurons across multiple brain areas. Yet, methodological constraints have led to a focus on individual cells or small groups of neurons in isolated brain regions. Dense recordings of neuronal population activity across brain regions would not only uncover rare cell and response types that have been missed by single-cell recordings – they would also enable the study of population-level representations, topology, and inter-area interactions.The goal of the proposed project is to understand how acoustic information is transformed by neuronal populations across successive processing steps of the vertebrate auditory pathway. To achieve this goal we will take advantage of the unique properties of the transparent vocalizing fish Danionella translucida, allowing us for the first time to densely measure neuronal population activity across the entire auditory system of an adult vertebrate. We aim to map the auditory anatomy of Danionella using targeted application of neural tracers, tissue clearing and whole-brain imaging. This will then serve as basis for whole-brain functional two-photon imaging of sensory-evoked neuronal population activity across the auditory pathway. Finally, we will combine functional imaging with tracing in order to identify and monitor the activity of projection neurons and their downstream target brain areas.If successful, this study will establish Danionella as the first adult vertebrate model organism with full optical access to its entire auditory processing chain and it will provide important insights into structure and function of the vertebrate auditory pathway at the population level.