Covert sleep-related biological processes are revealed by probabilistic analysis in Drosophila

Abstract

Sleep pressure and sleep depth are key regulators of wake and sleep. Current methods of measuring these parameters in Drosophila melanogaster have low temporal resolution and/or require disrupting sleep. Here we report analysis tools for high-resolution, noninvasive measurement of sleep pressure and depth from movement data. Probability of initiating activity, P(Wake), measures sleep depth while probability of ceasing activity, P(Doze), measures sleep pressure. In vivo and computational analyses show that P(Wake) and P(Doze) are largely independent and control the amount of total sleep. We also develop a Hidden Markov Model that allows visualization of distinct sleep/wake substates. These hidden states have a predictable relationship with P(Doze) and P(Wake), suggesting that the methods capture the same behaviors. Importantly, we demonstrate that both the Doze/Wake probabilities and the sleep/wake substates are tied to specific biological processes. These metrics provide greater mechanistic insight into behavior than measuring the amount of sleep alone.

Quantitative investigation reveals distinct phases in Drosophila sleep

“…The sleep pattern we found can also explain why P(Wake) changes along the day and especially showed two peaks around ZT0 and ZT12 in the previous study (see Fig. 1b and c in Wiggin, T. D., et al 39 ). Around those times, the flies move frequently and have mainly shorter rest time, the average level of P(Wake) should then be larger according to P(Wake) ≈ β / t .…”

“…It considers the relationship between the precious sleep state and the next sleep state and captures the properties of stage transition of sleep behavior. It is also a promising model for sleep behavior analysis in flies, and as reported the probability of initiating activity (P(Wake)) and the probability of ceasing activity (P(Doze)) could give a relative measure of sleep 39 . But when applying the DHHM model, those studies hypothesized that the current state is only affected by the previous state in the last time window (short memory).…”

A Paradoxical Kind of Sleep in Drosophila melanogaster

“…Our calcium imaging experiments support the view that spontaneous sleep in Drosophila is dynamic. 26,31,34,45 We uncovered different sleep stages, including an early ''wake-like'' active stage and a later, less-active ''deep'' sleep stage. Interestingly, wake-like sleep is often preceded by ''sleep-like wake'' (consistent with an earlier study), 46 showing that either behavioral state Article can be confounded at the level of brain activity.…”

Rest is Required to Learn an Appetitively-Reinforced Operant Task inDrosophila

“…6). This failure to promote learning could be due to induced rest not promoting the learning-associated sleep state (Liu et al, 2019;Wiggin et al, 2020), or it could also be the case that the precise timing of rest is important to its learning-associated function. We refined this hypothesis to instead propose that rest acts as a gate to learning.…”

“…However, we do not find that optogenetically-induced rest promotes learning (Figure 6). This failure to promote learning could be due to optogenetically-induced rest not promoting the learning-associated sleep state (Liu et al, 2019;Wiggin et al, 2020), as the brain-state of flies with dFSB-induced sleep is significantly different from the brain-state of spontaneous sleep (Tainton-Heap et al, 2020). It is also possible that the precise timing of rest is important to its learning-associated function and the timing of optogenetically-induced rest is suboptimal.…”