Many animal species generate acoustic signals for social communication and are faced with the challenge to distinguish external from self-generated sounds. How does the brain accomplish this when all sounds are coming in through the ear? It requires that self- generated and external sounds are separated at some point in the central auditory system. Copies of motor commands indicate to auditory brain areas when self-generated sounds are expected to arrive. This feedforward signaling suppresses neural responses in primary auditory nuclei, as well as the auditory cortex. Neurons that are activated with self- vocalization are also found in the auditory cortex. Yet, how the signal arrives there and where along the auditory processing pathway neural encoding of self-generated and external sounds diverge, is largely unknown. These are challenging questions to address because single-cell activity needs to be recorded simultaneously across several distant brain regions. This is currently only possible with fluorescent imaging techniques, but adult vertebrate brain tissue is too opaque for large-scale optical access. Danionella translucida (DT) is a transparent, miniature fish that vocalizes in social contexts and is therefore uniquely suitable for studying whole-brain activity of auditory processing during self- vocalization. Here I propose to generate an unbiased, whole-brain map of neural activity correlated with vocal self-representation and its cancellation. For this, I will establish stimulations of fictive vocalizations in DT and combine these with auditory playback while performing whole-brain calcium imaging. This data will offer unprecedented insights into vocal-auditory interactions across a vertebrate brain.
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