Graphical Abstract Highlights d Drosophila R5 network exhibits sleep-regulating compound slow-wave oscillations d Activation of circadian pathways mediates R5 multi-unit synchronization d Synchronization and compound delta oscillations require NMDAR coincidence detection d Eliminating NMDAR coincidence detection in R5 disrupts sleep In Brief Raccuglia et al. discover sleep-regulatory compound delta oscillations within the Drosophila R5 network. NMDAR coincidence detection mediates singleunit synchronization, which is the mechanistic basis for generating compound delta oscillations. Eliminating NMDAR coincidence detection, and thus compound oscillations, disrupts sleep and facilitates wakening. SUMMARYSlow-wave rhythms characteristic of deep sleep oscillate in the delta band (0.5-4 Hz) and can be found across various brain regions in vertebrates. Across phyla, however, an understanding of the mechanisms underlying oscillations and how these link to behavior remains limited. Here, we discover compound delta oscillations in the sleep-regulating R5 network of Drosophila. We find that the power of these slowwave oscillations increases with sleep need and is subject to diurnal variation. Optical multi-unit voltage recordings reveal that single R5 neurons get synchronized by activating circadian input pathways. We show that this synchronization depends on NMDA receptor (NMDAR) coincidence detector function, and that an interplay of cholinergic and glutamatergic inputs regulates oscillatory frequency. Genetically targeting the coincidence detector function of NMDARs in R5, and thus the uncovered mechanism underlying synchronization, abolished network-specific compound slow-wave oscillations. It also disrupted sleep and facilitated light-induced wakening, establishing a role for slow-wave oscillations in regulating sleep and sensory gating. We therefore propose that the synchronization-based increase in oscillatory power likely represents an evolutionarily conserved, potentially ''optimal,'' strategy for constructing sleep-regulating sensory gates.
Slow-wave rhythms characteristic of deep sleep oscillate in the delta band (0.5 -4 Hz) andcan be found across various brain regions in vertebrates. Across systems it is however unclear how oscillations arise and whether they are the causal functional unit steering behavior. Here, for the first time in any invertebrate, we discover sleep-relevant delta oscillations in Drosophila.We find that slow-wave oscillations in the sleep-regulating R2 network increase with sleep need. Optical multi-unit voltage recordings reveal that single R2 neurons get synchronized by sensory and circadian input pathways. We show that this synchronization depends on NMDA receptor (NMDARs) coincidence detector function and on an interplay of cholinergic and glutamatergic inputs setting a resonance frequency. Genetically targeting the coincidence detector function of NMDARs in R2, and thus the uncovered mechanism underlying synchronization, abolished network-specific slow-wave oscillations. It also disrupted sleep and facilitated light-induced wakening, directly establishing a causal role for slow-wave oscillations in regulating sleep and sensory gating. We therefore propose that the synchronization-based increase in oscillatory power likely represents an evolutionarily conserved, potentially 'optimal', strategy for constructing sleep-regulating sensory gates. that these delta oscillations depend on multi-unit synchronization mediated through NMDA receptor (NMDAR) coincidence detection. Disrupting this synchronization and thus the emergence of compound delta oscillations disrupts sleep and alters sensory gating during sleep. We thus identify slow-wave oscillations as an electrophysiological correlate for sleep regulation in invertebrates and place these oscillatory patterns at the basis of behavior. The sleep-regulating oscillations are comparable to sleep-regulating thalamic oscillations 20-22 as well as network-specific oscillations observed during sleep deprivation in vertebrates (local sleep) 2,23,24 . Our work demonstrates that slow-wave oscillations and sleep are fundamentally interconnected across systems, potentially representing an evolutionarily conserved strategy for network mechanisms regulating internal states and sleep. Results Sleep deprivation increases network-driven delta oscillations in the sleep-regulating R2 networkExamples of rhythmic activity patterns have previously been reported in insects 9,10 .However, their source, function and interdependence with internal states (such as sleep drive), remain largely unclear. We targeted expression of the GEVI ArcLight specifically to R2 neurons in the Drosophila brain. This defined network of 10 cells per hemisphere (Fig. 1a) resides within the ellipsoid body and is involved in sleep regulation [14][15][16] and multi-sensory relay [17][18][19] .In vivo recordings of the dendritic processes (bulb) of R2 neurons (Fig. 1a) identified electrical compound activity (Fig. 1b) that oscillated at delta-band frequencies between 0.5-1.5 Hz (Fig. 1b, d) in rested flies. We sleep-deprived f...
In vertebrates, several forms of memory-relevant synaptic plasticity involve postsynaptic rearrangements of glutamate receptors. In contrast, previous work indicates that Drosophila and other invertebrates store memories using presynaptic plasticity of cholinergic synapses. Here, we provide evidence for postsynaptic plasticity at cholinergic output synapses from the Drosophila mushroom bodies (MBs). We find that the nicotinic acetylcholine receptor (nAChR) subunit α5 is required within specific MB output neurons (MBONs) for appetitive memory induction, but is dispensable for aversive memories. In addition, nAChR α2 subunits mediate memory expression and likely function downstream of α5 and the postsynaptic scaffold protein Dlg. We show that postsynaptic plasticity traces can be induced independently of the presynapse, and that in vivo dynamics of α2 nAChR subunits are changed both in the context of associative and non-associative (familiarity) memory formation, underlying different plasticity rules. Therefore, regardless of neurotransmitter identity, key principles of postsynaptic plasticity support memory storage across phyla.
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