Sleep pressure regulates mushroom body neural-glial interactions in Drosophila

Abstract

Sleep is a behavior that exists broadly across animal phyla, from flies to humans, and is necessary for normal brain function. Recent studies in both vertebrates and invertebrates have suggested a role for glial cells in sleep regulatory processes. Changes in neural-glial interactions have been shown to be critical for synaptic plasticity and circuit function. Here, we wanted to test the hypothesis that changes in sleep pressure alters neural-glial interactions. In the fruit fly, Drosophila melanogaster, sleep is known to be regulated by mushroom body (MB) circuits. We used the technique GFP Reconstitution Across Synaptic Partners (GRASP) to test whether changes in sleep pressure affect neural-glial interactions between MB neurons and astrocytes, a specialized glial cell type known to regulate sleep in flies and mammals. The MB-astrocyte GRASP signal was reduced after 24 h of sleep deprivation, whereas the signal returned to baseline levels following 72 h of recovery. Social enrichment, which increases sleep drive, similarly reduced the MB-astrocyte GRASP signal. We did not observe any changes in the MB-astrocyte GRASP signal over time-of-day, or following paraquat exposure or starvation. These data suggest that changes in sleep pressure are linked to dynamic changes in neural-glial interactions between astrocytes and neuronal sleep circuits, which are not caused by normal rest-activity cycles or stressors.

Sleep deprivation results in diverse patterns of synaptic scaling across the Drosophila mushroom bodies

“…Connections between neurons in the MB may be also influenced by non-neuronal cell types, including astrocytes. Astrocytic contact with KCs can be reduced by sleep loss 105 and astrocytic calcium levels correlate with sleep pressure, 106 which both suggest that astrocytic processes could be positioned to mediate sleepdependent plasticity in the MB.…”

Drosophila Glia: Models for Human Neurodevelopmental and Neurodegenerative Disorders

“…The released gliotransmitters bind to presynaptic and postsynaptic receptors to regulate synaptic transmission, the disruption of which results in neuronal dysfunction and abnormal behaviors in animal models [120,121]. The use of genetic techniques has revealed that Drosophila astrocytic glial cells are also critical for the neural circuits regulating circadian behavior and sleep [122][123][124]. D-serine and its neuronal receptor have been implicated in sleep regulation in both flies and mammals [125][126][127].…”

AANAT1 functions in astrocytes to regulate sleep homeostasis

“…Astrocytes are particularly well-suited for regulating sleep in this way because they have ramified processes that infiltrate neuropil regions to lie in close proximity to synapses. SD can seemingly reduce the degree of contact between astrocytes and neurons in the fly brain ( Vanderheyden et al, 2019 ), and so it is possible that these structural changes could influence monoamine uptake and inactivation by astrocytes.…”