When hungry, simple foods can seem delicious. When full, even the most tempting dishes lose their appeal. In brief, our perception of the sensory world depends on how we sense our body. Does such interoception also play a role when we are asleep? During sleep, sensory stimuli from the environment are poorly tracked, and arousal thresholds are high. Currently, very little is known about the diversity of interoceptive signaling during sleep, and we lack a neural fundament to decide whether interoception interacts with sleep’s restorative and beneficial functions. My thesis is a contribution to the question of how interoceptive stimuli influence the regulation of mammalian sleep and its processing by the sleeping brain, focusing on a major body-brain connection, the vagus nerve.
The goal of this study was to characterize the physiological state of the sleeping mouse induced by vagal sensory stimulation in both its bodily and brain correlates and to identify some of its underlying mechanisms. Anatomical evidence indicates that stimulating sensory inputs from interoceptive systems would not only recruit autonomic feedback loops but also target central sites for the regulation of sleep-wake behavior. I demonstrate that this stimulation modulates sleep architecture and its spectral composition by inducing a non-rapid eye-movement (NREMS)-like state and preventing the occurrence of rapid-eye movement sleep (REMS) without affecting its regulatory mechanisms. Additionally, I find that vagal sensory stimulation induces a brain-body cooling, possibly due strengthened parasympathetic activity (vasodilation and heat loss) and/or activation of hypothalamic nuclei involved in temperature regulation. I provide evidence that a potential neuronal mechanism underlying this regulation could also be through the locus coeruleus (LC), receiving indirect innervation from the nucleus tractus solitarius (NTS) and known to suppress REMS when activated. These findings make me conclude that vagal sensory afferents powerfully regulate sleep by targeting several of its major physiological correlates in brain and body. Moreover, my findings further point out that the brain-body state induced by vagal sensory stimulation can be described as a novel sleep-like state where brain-body cooling is exacerbated while LC activity strengthened. These observations reveal a major role for vagal afferent activity in body-brain physiology, which contributes to maintaining a balanced expression of NREMS and REMS through brain-body cooling. This highlights the importance of considering bodily processes when studying sleep regulation.
Together, my work shows that vagal sensory stimulation could help fine-tune temperature and neuromodulatory conditions during sleep, potentially improving sleep quality and enhancing cognitive functions. These findings also contribute to expanding our understanding of the clinical effects of vagus nerve stimulation (VNS), a widely used technique in humans for treating various neurological conditions.