Effects of associative learning on neuronal activity in the entire adult vertebrate brain

• Applicant: Daniil Markov, Ph.D.
• Subject Area: Cognitive, Systems and Behavioural Neurobiology ; Experimental and Theoretical Network Neuroscience
• Term: since 2023
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 531605337

Experience affects how our brains process sensory information. When an animal learns that a stimulus predicts a reward, the neuronal response to that stimulus changes in many regions of the brain. Although numerous details on such changes have been revealed in recent decades, our understanding of the effects of learning on neuronal activity remains fragmented. This is because our current knowledge is mostly based on single-unit recordings or functional imaging of small neuronal populations in selected subregions of the brain. Such approach is not only prone to bias due to the preselection of candidate regions, but also insufficient for understanding how different regions interact with each other during learning. To address this gap, this project will investigate how learning alters neuronal activity throughout the entire brain. This can be achieved using whole-brain calcium imaging. However, until recently, the only vertebrate suitable for this method was the larval zebrafish, whose ability to learn through conditioning is very limited. Here, I will take advantage of a new model organism, the miniature fish Danionella cerebrum (DC). Fish of this species are transparent and have the smallest known adult vertebrate brain, which allows to monitor activity of all its neurons using functional imaging. Furthermore, despite their small size, they can learn complex behaviors through Pavlovian conditioning. This combination creates a unique opportunity to study the effects of learning on neuronal activity throughout the brain. I will train the fish in a conditioning assay and monitor the activity of their neurons before and after learning using whole-brain imaging. This will allow me to characterize the effects of learning on neuronal activity throughout the brain. I will then train the animals to associate the same stimulus with two different meanings: food or threat, and compare learning-induced changes in activity between these two cases. This will allow me to identify, which of the observed effects reflect the exact learned meaning of the stimulus, and which, in turn, reflect non-specific phenomena such as sensitization of the sensory system to a relevant stimulus. If successful, this project will characterize how activity of each individual neuron within the vertebrate brain changes upon learning. I expect that such holistic and unbiased approach will provide important insights into the effects of experience on sensory processing across brain-wide distributed circuits. In addition, the project will establish DC as the first vertebrate with optical access to brain-wide experience-dependent changes in neuronal activity.

• DFG Programme: Research Grants