Manipulations of the olfactory circuit highlight the role of sensory stimulation in regulating sleep amount

Abstract Study Objectives While wake duration is a major sleep driver, an important question is if wake quality also contributes to controlling sleep. In particular, we sought to determine whether changes in sensory stimulation affect sleep in Drosophila. As Drosophila rely heavily on their sense of smell, we focused on manipulating olfactory input and the olfactory sensory pathway. Methods Sensory deprivation was first performed by removing antennae or applying glue to antennae. We then measured sleep in response to neural activation, via expression of the thermally gated cation channel TRPA1, or inhibition, via expression of the inward rectifying potassium channel KIR2.1, of subpopulations of neurons in the olfactory pathway. Genetically restricting manipulations to adult animals prevented developmental effects. Results We find that olfactory deprivation reduces sleep, largely independently of mushroom bodies that integrate olfactory signals for memory consolidation and have previously been implicated in sleep. However, specific neurons in the lateral horn, the other third-order target of olfactory input, affect sleep. Also, activation of inhibitory second-order projection neurons increases sleep. No single neuronal population in the olfactory processing pathway was found to bidirectionally regulate sleep, and reduced sleep in response to olfactory deprivation may be masked by temperature changes. Conclusions These findings demonstrate that Drosophila sleep is sensitive to sensory stimulation, and identify novel sleep-regulating neurons in the olfactory circuit. Scaling of signals across the circuit may explain the lack of bidirectional effects when neuronal activity is manipulated. We propose that olfactory inputs act through specific circuit components to modulate sleep in flies.