Vladyslav Vyazovskiy - Neuroscience - 'Renormalization of aging brain networks by sleep enhancement with psychedelics'

Population ageing brings significant challenges to society and the economy. Sleep and cognitive problems are among the major complaints of the elderly, and insufficient or disrupted sleep has been linked to a broad range of neurological and neurodegenerative disorders. One of the most notable examples is Alzheimer’s disease, which has been directly linked with sleep disruption, and has no cure. It has been proposed that improving or enhancing sleep could have far-reaching health benefits beyond the improvement of sleep per se. Age-related changes in cognitive functions encompass a reduced capacity to learn new facts and skills (plasticity), as well as attentional and memory problems. It is well established that cortical synapses and firing rates are dynamically modulated by intrinsic, naturally occurring processes, of which sleep is of key significance. For instance, evidence suggests that during sleep some synaptic connections are strengthened, while others are weakened or eliminated, to allow bringing the overall synaptic strength to its homeostatic set point. Sleep also plays an important role in memory consolidation. According to the prevailing view, sleep and associated large-scale network oscillations, such as slow waves and sleep spindles, are necessary for the transfer of temporary memory traces from the hippocampus for long-term storage in the cortex, where they are integrated into existing memory schemata. Sleep disruption prevents consolidation of recent memories, and equally importantly, severely reduces the capacity for further learning. There is a great deal of interest in developing new approaches to improve sleep quality or enhance brain oscillations during sleep, and the possibility of non-invasive modulation of sleep oscillations has recently attracted significant attention. However, research in this areas is still rudimentary, and studies often yield contradictory results. It is well established that both sleep and psychedelic drugs exert a profound effect on neural activity across the brain, including changes to neuronal firing rates and the strength of synaptic connections. Our recent data suggest that in laboratory mice 5-MeO DMT and psilocin induce an altered state of vigilance, characterised by an intrusion of slow-wave activity – the key hallmark of NREM sleep – in the awake state. This finding is highly relevant given the established functional role of sleep in general, and slow-wave activity in particular in a broad range of restorative processes – from synaptic renormalisation to clearance of toxic by-products of metabolism. Not surprisingly, there are many studies currently underway aiming to artificially enhance sleep slow waves for therapeutic benefit. However, to the best of our knowledge, the possibility of using psychedelics as a tool to promote restorative processes in the brain in the context of ageing, and its associated risk for cognitive decline and neurodegeneration, has not been explored. We propose that enhancement of slow waves by psychedelics can restore the capacity for synaptic plasticity, which is especially relevant in the context of the ageing brain. My laboratory has a unique combination of relevant expertise – from fundamental sleep neurobiology, including sleep in ageing, to synaptic plasticity, psychedelics and closed-loop modulation of brain activity during sleep. We benefit from a highly stimulating interdisciplinary environment at DPAG, SCNi and KIND, and a long-term collaboration with Beckley Psytech Ltd. The proposed research has a strong potential to provide essential knowledge which will be used to develop innovative therapies for restoring the potential for synaptic plasticity in the ageing brain.