The role of the 5-HT2A mediated neurotransmission in behaviour and neuronal dynamics during sleep and waking in mice

Serotonergic signalling in the brain is important for a broad range of functions - from appetite, thermoregulation, and sleep to anxiety, learning and memory. Studies suggest that manipulations of the serotonergic system can impact the amount and distribution of different vigilance states. For example, a nearly complete elimination of rapid eye movement (REM) sleep, as defined using conventional criteria, was observed after treatment with selective serotonin reuptake inhibitors in both humans and laboratory animals. Surprisingly, the loss of REM sleep does not appear to lead to any overt negative consequences. This suggests either that REM sleep does not have any biological function, or that potentiating serotonergic system results in an occurrence of altered or hybrid states of vigilance that can functionally replace the bona fide REM sleep. If the latter were true, then a key role of the serotonergic system is in controlling the quality, rather than quantity of specific sleep states. The aim of this project is to characterise the effects of 5-HT2A agonists on cortical neural activity and behaviour in freely moving mice. This class of compounds was selected because our preliminary studies suggest their strong REM sleep - suppressing effects in mice. In this study we shall perform chronic electrophysiological recordings from the neocortex in freely moving mice, combined with EMG, accelerometery, positional eye tracking and pupil diameter across spontaneous wakefulness and sleep, as well as during behavioural task performance during and after administration of psilocin and other 5-HT2A ligands. This project will for the first time characterise the effects of 5-HT2A agonists on both sleep and wake quantity and quality, establish novel metrics of behavioural arousal and its electrophysiological correlates in freely behaving mice in accordance with the 3Rs, and address the relationship between REM sleep and attentional performance.