Temporal drift of sleep-wake representations in hypothalamic neuronal ensembles
TL;DR
Although single-cell state selectivity drifts over days, the overall ensemble representations remain stable and are altered by diazepam, indicating that while individual neurons exhibit dynamic, state-dependent shifts of their activity, the overall organization of sleep-wake neural populations remains stable.
Abstract
Correlative and causal evidence implicates distinct genetically-defined and evolutionary-conserved hypothalamic neurons in regulating wakefulness, non-rapid eye movement (NREM), and rapid eye movement (REM) sleep. The prevailing view is that these circuits govern sleep-wake states by recruiting stable, invariant neuronal substrates, yet, this remains unknown. Here, we show that inhibitory, excitatory, hypocretins/orexins-, and melanin concentrating hormone-expressing neurons in hypothalamus did not exhibit stable state-specific activities using longitudinal single cell calcium imaging in freely-moving, sleeping male mice. Instead, their activity patterns shift across sleep-wake states over time, while the distribution of active neurons in each sleep state remains stable. While sleep deprivation minimally affected the selectivity of these activity patterns, we found that the sleep-promoting drug diazepam recruited NREM sleep-active cells that were previously inactive or wake-active. These findings indicate that while individual neurons exhibit dynamic, state-dependent shifts of their activity, the overall organization of sleep-wake neural populations remains stable. Hypothalamic neurons encode sleep–wake states, but their long-term stability is unclear. Here, authors show that although single-cell state selectivity drifts over days, the overall ensemble representations remain stable and are altered by diazepam.