Revealing the Neural Population Code of Auditory Space by Large-Volume Ca2+ Imaging in the Mouse

• Applicant: Dr. Robert Prevedel
• Subject Area: Experimental and Theoretical Network Neuroscience
• Term: since 2021
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 458898724

Our sensory systems have the remarkable ability of interpreting very distinct types of information carried by sensory stimuli. An extraordinary example of this is the ability of our auditory system to interpret spatial information carried by sounds. Being able to locate a sound source is crucially important for animals to e.g. find preys or avoid danger. In humans, this ability is particularly compromised in severe hearing loss patients, which incentivises efforts to better understand how auditory spatial information is represented (‘encoded’) and transmitted throughout the different levels of the auditory pathway.The responses of neurons tuned to sound location cues throughout the auditory pathway has extensively been described. However, the information encoded by single neurons is limited as they are typically noisy and widely tuned to sound location. Therefore, the accurate and stable representation of this information more likely depends on a concerted activity of populations of neurons. A core region in the auditory pathway to study this is the inferior colliculus (IC), where ascending and descending inputs carrying sound location information converge. How this information is integrated into structured population responses (‘population code’), and decoded at higher order relays of IC, remains to be elucidated. Therefore, in this proposal we aim to determine how the location of a sound source in the horizontal plane (azimuth) is encoded in the neuronal population responses from the IC in mice. However, since these responses are typically distributed over very large tissue volumes, identifying and linking them with perception remained experimentally challenging so far with current technology.To address this major challenge, here we will adapt an ultra-fast 3D calcium imaging method recently developed in our lab. This will allow us to present sound stimuli carrying sound location cues in azimuth to head fixed mice while simultaneously sampling neuronal population activity of thousands of neurons covering a 0.5x0.5x0.5mm volume at the IC with single cell resolution.To identify this neural code, i.e. how the recorded responses of IC neuronal populations relate to presented sound azimuth, we will use advanced functional clustering analysis techniques. This will allow us to explore how the information represented by IC population activity could be decoded by higher order relays of the auditory pathway and to compare the performance of different theoretical decoding models currently discussed in the field. The outcome of this project will constitute the first characterization of the neural population code of sound azimuth at the mammalian IC. Additionally, it will provide substantial insight into how this representation could be decoded by higher order neurons. Altogether, our findings could contribute to the design of new and improved neuroprosthetics, like auditory midbrain implants, to aid patients with severe hearing loss.

• DFG Programme: Research Grants
• International Connection: France, Italy
• Cooperation Partners: Dr. Hiroki Asari; Dr. Brice Bathellier