Neural oscillations and circuit interactions constructing selective sensory gates for sleep regulation

• Applicant: Davide Raccuglia, Ph.D.
• Subject Area: Cognitive, Systems and Behavioural Neurobiology ; Experimental and Theoretical Network Neuroscience ; Molecular Biology and Physiology of Neurons and Glial Cells
• Term: since 2021
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 462539941

Sleep disruption is a hallmark of insomnia and severely diminishes sleep quality, which is linked to depression and deficits in attention and learning. To maintain sleep, neural networks in our brains create selective sensory “gates” that block sensory information while we are asleep. Since sleep is a phenomenon widely conserved throughout the animal kingdom, it is likely that all animals share similar strategies to filter sensory information. However, the fundamental neurophysiological principles and neural interactions behind the creation of selective sensory gates for sleep regulation are essentially unknown. During sleep in mammals, reptiles and even in Zebrafish, neural networks undergo large-scale synchronizations of slow-wave oscillatory activity (SWO). Interestingly, cognitive impairments in sleep deprived but awake mammals have been linked to local synchronizations of SWO in specific neural networks, indicating a role for SWO in shutting down sensory processing and signaling sleep need. In a recent study, we used genetically encoded voltage indicators to discover that even in the evolutionary distant fruit fly Drosophila melanogaster electrical SWO play an important role in the regulation of sleep drive and sensory gating. We found that sleep drive mediating R5 neurons synchronize their electrical patterns to generate network-specific SWO that facilitate consolidated sleep phases. Our findings suggest that SWO might be an evolutionary optimized strategy to block sensory information and provide consolidated sleep. However, the underlying neural interactions and neurophysiological principles that could explain how SWO create selective sensory gates remain unclear.In Drosophila, the less complex brain, unprecedented genetic accessibility and the sleep-related physiological analogies offer a unique opportunity to study the essential components needed to construct selective sensory gates. I therefore propose to use state-of-the-art genetic tools combining optical electrophysiology, analytical tools we pioneered, optogenetics and behavioral paradigms to understand at a neurophysiological level how SWO and the underlying neural interactions can block sensory information to provide adequate sleep quality. Specifically, we will focus on a recurrent circuitry composed of R5 neurons, Helicon cells and the dorsal fan-shaped body to investigate how synaptic interactions between these neurons synchronize neural activity patterns and provide the neurophysiological framework to construct sensory gates. The proposed project will broaden our understanding about the neural mechanisms of sensory gating and the neural interactions needed for a good night’s sleep.

• DFG Programme: Research Grants