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

Jacqueline T Weiss,Jeffrey M Donlea

doi:10.1016/j.cub.2021.05.018

Abstract

Sleep is essential for a variety of plastic processes, including learning and memory. However, the consequences of insufficient sleep on circuit connectivity remain poorly understood. To better appreciate the effects of sleep loss on synaptic connectivity across a memory-encoding circuit, we examined changes in the distribution of synaptic markers in the Drosophila mushroom body (MB). Protein-trap tags for active zone components indicate that recent sleep time is inversely correlated with Bruchpilot (BRP) abundance in the MB lobes; sleep loss elevates BRP while sleep induction reduces BRP across the MB. Overnight sleep deprivation also elevated levels of dSyd-1 and Cacophony, but not other pre-synaptic proteins. Cell-type-specific genetic reporters show that MB-intrinsic Kenyon cells (KCs) exhibit increased pre-synaptic BRP throughout the axonal lobes after sleep deprivation; similar increases were not detected in projections from large interneurons or dopaminergic neurons that innervate the MB. These results indicate that pre-synaptic plasticity in KCs is responsible for elevated levels of BRP in the MB lobes of sleep-deprived flies. Because KCs provide synaptic inputs to several classes of post-synaptic partners, we next used a fluorescent reporter for synaptic contacts to test whether each class of KC output connections is scaled uniformly by sleep loss. The KC output synapses that we observed here can be divided into three classes: KCs to MB interneurons; KCs to dopaminergic neurons; and KCs to MB output neurons. No single class showed uniform scaling across each constituent member, indicating that different rules may govern plasticity during sleep loss across cell types.

Highlights

BRP abundance in mushroom body (MB) lobes is inversely related with recent sleep time To examine the consequences of sleep loss on MB synaptic connections, we first observed the abundance of GFP-tagged BRP expressed from a MiMIC protein trap insertion into an intron of the Brp locus.[56,57]
The BRP::GFP signal increased by 32%–46% in each MB lobe from sleep-deprived brpMI02987-GFSTF/+ flies compared to controls (Figures 1A and 1B), supporting previous reports of increased pre-synaptic terminal size in MB neurons.[16]
We find that abundance of Brp, dSyd-1, and Cacophony broadly increase across all MB lobes after overnight sleep deprivation and that acutely increasing sleep for 6 h is sufficient to reduce Brp levels across the a, b, g, and b’ lobes

Summary

Introduction

In a variety of species, sleep supports the capacity for new learning and is vital for the consolidation of recently formed memories.[1,2,3,4,5,6] In Drosophila melanogaster, overnight sleep loss is sufficient to impair acquisition of new associative memories that are encoded in the mushroom bodies (MBs),[3] and sleep disruptions that follow learning can prevent memory consolidation.[2,7] Interestingly, sleep is often elevated or intensified during conditions of heightened synaptic reorganization, including early development,[8,9,10] recovery from neural injury,[11,12] and memory consolidation.[1,2] Together, these results indicate that sleep may support plastic remodeling in the brain. The consequences of sleep disruptions on synaptic connectivity, are not clearly understood. Indicate that sleep deprivation may either weaken or prevent the expansion of synaptic connections in some circuits.[9,23,24,25] These previous studies demonstrate that sleep disruption alters synaptic abundance or size in several neuronal cell types, but it is unclear whether sleep loss uniformly affects all classes of neurons or synapses within a given circuit

Methods

Results

Discussion

Conclusion