Pathway-dependent regulation of sleep dynamics in a network model of the sleep-wake cycle

Sleep is a fundamental homeostatic process within the animal kingdom. Although various brain areas and cell types are involved in the regulation of the sleep-wake cycle, it is still unclear how different pathways between neural populations contribute to its regulation. Here we address this issue by investigating the behavior of a simplified network model upon synaptic weight manipulations. Our model consists of three neural populations connected by excitatory and inhibitory synapses. Activity in each population is described by a firing-rate model, which determines the state of the network. Namely wakefulness, rapid eye movement (REM) sleep or non-REM (NREM) sleep. By systematically manipulating the synaptic weight of every pathway, we show that even this simplified model exhibits non-trivial behaviors: for example, the wake-promoting population contributes not just to the induction and maintenance of wakefulness, but also to sleep induction. Although a recurrent excitatory connection of the REM-promoting population is essential for REM sleep genesis, this recurrent connection does not necessarily contribute to the maintenance of REM sleep. The duration of NREM sleep can be shortened or extended by changes in the synaptic strength of the pathways from the NREM-promoting population. In some cases, there is an optimal range of synaptic strengths that affect a particular state, implying that the amount of manipulations, not just direction (i.e., activation or inactivation), needs to be taken into account. These results demonstrate pathway-dependent regulation of sleep dynamics and highlight the importance of systems-level quantitative approaches for sleep-wake regulatory circuits.\n\nAuthor SummarySleep is essential and ubiquitous across animal species. Over the past half-century, various brain areas, cell types, neurotransmitters, and neuropeptides have been identified as part of a sleep-wake regulating circuitry in the brain. However, it is less explored how individual neural pathways contribute to the sleep-wake cycle. In the present study, we investigate the behavior of a computational model by altering the strength of connections between neuronal populations. This computational model is comprised of a simple network where three neuronal populations are connected together, and the activity of each population determines the current state of the model, that is, wakefulness, rapid-eye-movement (REM) sleep or non-REM (NREM) sleep. When we alter the connection strength of each pathway, we observe that the effect of such alterations on the sleep-wake cycle is highly pathway-dependent. Our results provide further insights into the mechanisms of sleep-wake regulation, and our computational approach can complement future biological experiments.