TY - JOUR
T1 - Sleep drive is encoded by neural plastic changes in a dedicated circuit
AU - Liu, Sha
AU - Liu, Qili
AU - Tabuchi, Masashi
AU - Wu, Mark N.
N1 - Publisher Copyright:
© 2016 Elsevier Inc. All rights reserved.
PY - 2016/6/2
Y1 - 2016/6/2
N2 - Prolonged wakefulness leads to an increased pressure for sleep, but how this homeostatic drive is generated and subsequently persists is unclear. Here, from a neural circuit screen in Drosophila, we identify a subset of ellipsoid body (EB) neurons whose activation generates sleep drive. Patch-clamp analysis indicates these EB neurons are highly sensitive to sleep loss, switching from spiking to burst-firing modes. Functional imaging and translational profiling experiments reveal that elevated sleep need triggers reversible increases in cytosolic Ca2+ levels, NMDA receptor expression, and structural markers of synaptic strength, suggesting these EB neurons undergo "sleep-need"-dependent plasticity. Strikingly, the synaptic plasticity of these EB neurons is both necessary and sufficient for generating sleep drive, indicating that sleep pressure is encoded by plastic changes within this circuit. These studies define an integrator circuit for sleep homeostasis and provide a mechanism explaining the generation and persistence of sleep drive.
AB - Prolonged wakefulness leads to an increased pressure for sleep, but how this homeostatic drive is generated and subsequently persists is unclear. Here, from a neural circuit screen in Drosophila, we identify a subset of ellipsoid body (EB) neurons whose activation generates sleep drive. Patch-clamp analysis indicates these EB neurons are highly sensitive to sleep loss, switching from spiking to burst-firing modes. Functional imaging and translational profiling experiments reveal that elevated sleep need triggers reversible increases in cytosolic Ca2+ levels, NMDA receptor expression, and structural markers of synaptic strength, suggesting these EB neurons undergo "sleep-need"-dependent plasticity. Strikingly, the synaptic plasticity of these EB neurons is both necessary and sufficient for generating sleep drive, indicating that sleep pressure is encoded by plastic changes within this circuit. These studies define an integrator circuit for sleep homeostasis and provide a mechanism explaining the generation and persistence of sleep drive.
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U2 - 10.1016/j.cell.2016.04.013
DO - 10.1016/j.cell.2016.04.013
M3 - Article
C2 - 27212237
AN - SCOPUS:84971508902
SN - 0092-8674
VL - 165
SP - 1347
EP - 1360
JO - Cell
JF - Cell
IS - 6
ER -