Visualizing synaptic homeostatic plasticity : linking synaptic changes during sleep with learning in Drosophila

• Applicant: Sridhar Jagannathan, Ph.D.
• Subject Area: Cognitive, Systems and Behavioural Neurobiology
• Term: from 2021 to 2024
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 467545627

Sleep is a fundamental physiological process conserved across the whole animal kingdom. While crucial for many behaviors – sleep deprivation causes lapses in attention and memory-retrieval– its core biological function remains one of the biggest mysteries of neurobiology. The synaptic homeostasis hypothesis proposes that sleep regulates synaptic plasticity, thereby facilitating learning. In this project, I will investigate how sleep deprivation disrupts synaptic plasticity in the genetically tractable Drosophila system. I will explore the interaction between sleep and synaptic scaling, memory, and attention processes using molecular and circuit readouts in the behaving animal. Odour memories are stored at synapses between Kenyon cells (KCs) and a small number of MB output neurons (MBONs). KC to MBON synapses are modulated by dopaminergic neurons (DANs) which assign valence to those odours. Experimental co-activation of DANs with odour can implant aversive or appetitive memories. I will co-activate DANs with odours to trigger aversive memories lasting for several days. First, I will record the strength and molecular composition of KC-MBON contacts over time along with the animals' memory performance following sleep-deprivation. Second, to investigate the effect of sleep-deprivation on attention and memory, I will use machine learning to classify KC activity and investigate whether odour representations are intact even memory retrieval is impaired. Third, I will link trial-by-trial MBON dynamics with behaviour. Finally, I will connect readouts of synaptic strength to MBON dynamics following sleep-deprivation to investigate how sleep modulates KC-MBON plasticity in the context of memory formation and learning.

• DFG Programme: WBP Position