Vladyslav Vyazovskiy - Neuroscience - 'Controlled hypometabolic state for resetting brain networks'

Hibernation is a widespread evolutionary strategy employed by many animal species to deal with adverse environmental conditions, such as food scarcity, low or high temperatures and climatic natural disasters. Hypometabolism is typically considered as an energy saving strategy, but it is employed acutely, for example in response to imminent threat, such as predation risk. Much research has been directed towards investigating peripheral bodily physiology during hibernation, but, surprisingly, the brain mechanisms of torpor, as well as the effects of hibernation on the brain remain under-investigated. Limited knowledge suggests that torpor represents a remarkable example of brain plasticity, reflected in massive synaptic remodelling upon entrance into and emergence from hibernation. Harnessing this capacity for human applications remains in its infancy. The proposed work will develop a novel approach, based on closed loop neuromodulation, which will enable a physiological induction of torpor, to investigate its effects on brain function, and to test the hypothesis that resetting brain networks through cycles of hibernation increases resilience to adverse conditions, including mental health conditions, such as PTSD and depression. In this project we aim to unravel physiological mechanisms involved in spontaneous entering of the state of hibernation in natural torpidators Phodopus sungorus. We will use a closed-loop approach where combined monitoring of brain activity and physiological parameters, such as levels of metabolism, body temperature and heart rate, will be dynamically coupled with relevant environmental factors, such as lighting, temperature and gaseous composition of air, to facilitate state transitions through stimulation of the brain and the autonomic nervous system in a physiologically relevant context. The key innovative element of this proposal is the new approach to harness hibernation-associated brain plasticity for treatment of mental health disorders, such as PTSD and depression. We will study how spontaneous and induced hypometabolism resets brain networks through synaptic remodelling, and investigate the role of sleep in homeostatic regulation of torpor-related synaptic plasticity.