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

Abstract

11 Sleep is a fundamental homeostatic process within the animal kingdom. Although various brain areas 12 and cell types are involved in the regulation of the sleep-wake cycle, it is still unclear how different 13 pathways between neural populations contribute to its regulation. Here we address this issue by 14 investigating the behavior of a simplified network model upon synaptic weight manipulations. Our 15 model consists of three neural populations connected by excitatory and inhibitory synapses. Activity in 16 each population is described by a firing-rate model, which determines the state of the network. Namely 17 wakefulness, rapid eye movement (REM) sleep or non-REM (NREM) sleep. By systematically 18 manipulating the synaptic weight of every pathway, we show that even this simplified model exhibits 19 non-trivial behaviors: for example, the wake-promoting population contributes not just to the induction 20 and maintenance of wakefulness, but also to sleep induction. Although a recurrent excitatory 21 connection of the REM-promoting population is essential for REM sleep genesis, this recurrent 22 connection does not necessarily contribute to the maintenance of REM sleep. The duration of NREM 23 sleep can be shortened or extended by changes in the synaptic strength of the pathways from the 24 NREM-promoting population. In some cases, there is an optimal range of synaptic strengths that affect 25 a particular state, implying that the amount of manipulations, not just direction (i.e., activation or 26 inactivation), needs to be taken into account. These results demonstrate pathway-dependent 27 regulation of sleep dynamics and highlight the importance of systems-level quantitative approaches for 28 sleep-wake regulatory circuits. 29 30 Author Summary 31 Sleep is essential and ubiquitous across animal species. Over the past half-century, various brain 32 areas, cell types, neurotransmitters, and neuropeptides have been identified as part of a sleep-wake 33 regulating circuitry in the brain. However, it is less explored how individual neural pathways contribute 34 to the sleep-wake cycle. In the present study, we investigate the behavior of a computational model by 35 altering the strength of connections between neuronal populations. This computational model is 36 comprised of a simple network where three neuronal populations are connected together, and the 37 activity of each population determines the current state of the model, that is, wakefulness, rapid-eye-38 movement (REM) sleep or non-REM (NREM) sleep. When we alter the connection strength of each 39 pathway, we observe that the effect of such alterations on the sleep-wake cycle is highly pathway-40 dependent. Our results provide further insights into the mechanisms of sleep-wake regulation, and our 41 computational approach can complement future biological experiments. 42 2 43 Introduction 44 Global brain states vary dynamically on multiple timescales. Humans typically exhibit a daily cycle 45 between three major behavioral states: wakefulness, REM sleep an...

Pathway-Dependent Regulation of Sleep Dynamics in a Network Model of the Sleep–Wake Cycle

“…We thank Arno Onken, William Berg, Aimee Bias, and Emma Mitchell for critical reading of the manuscript. This manuscript has been released as a Pre-Print at BioRxiv (Héricé and Sakata, 2019).…”