Neural basis of perceptual decision-making in larval zebrafish

• Applicant: Professor Dr. Armin Bahl, Ph.D.
• Subject Area: Cognitive, Systems and Behavioural Neurobiology
• Term: since 2020
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 429442687

It is a long-standing question in neuroscience how nervous systems accumulate sensory evidence and how they use such information to make reliable perceptual decisions about the next favorable motor action. Over the last few decades, primates have been the model organism of choice for addressing this problem, providing fundamental insights into the algorithmic nature of the behavior. These works have proposed that several brain areas are involved in the computation but recent manipulation studies are questioning these ideas, emphasizing the need for brain-wide explorations of the underlying circuit dynamics. By adapting a classical random dot motion discrimination paradigm, I have previously discovered that an animal as simple as the larval zebrafish can temporally integrate sensory information as well. The rich molecular genetic toolkit and modern imaging technologies available for this model organism now provide me with a unique opportunity to study the neural basis of perceptual decision-making in a level of detail that is currently impossible elsewhere. The main objective of this project proposal is to employ a combination of the available state-of-the-art methods in order to obtain an experimentally well-constrained ground truth of the neuronal circuit architecture underlying the behavior. To achieve this goal, I plan to work on four tightly connected research aims. I will first conduct various psychophysical experiments in larval zebrafish and build mathematical models based on measured behavior. I will then use two-photon brain-wide and regional imaging to verify already described brain regions implementing these computations and to expand over the whole brain. I will then employ state-of-the-art methods for creating precise maps of the identified regions, containing information about neurotransmitter identity and morphology. Together with functional characterizations on the level of single neurons and trials, this will allow me to propose and constrain local and brain-wide network models describing information flow from sensations to motor outputs. These models will make precise and testable predictions, which I will then explicitly explore using functionally targeted ablations and optogenetic activations of small populations of neurons. The proposed work should, thereby, provide key insights into the general computational principles of an important behavior, perceptual decision-making, and should significantly advance our understanding of a long-standing question in neuroscience.

• DFG Programme: Independent Junior Research Groups
• Major Instrumentation: Custom-built two-photon microscope
• Instrumentation Group: 5090 Spezialmikroskope