Differential activation of immune factors in neurons and glia contribute to individual differences in resilience/vulnerability to sleep disruption

Dissel, Stephane; Seugnet, Laurent; Thimgan, Matthew S.; Silverman, Neal S.; Angadi, Veena; Thacher, Pamela V; Burnham, Melissa M.; Shaw, Paul J.

doi:10.1016/j.bbi.2014.09.019

Cited by 45 publications

(55 citation statements)

References 48 publications

(86 reference statements)

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Curiously, few long-sleeping mutants have been evaluated for memory and we did not wish to use long-sleeping flies with memory impairments [52, 53]. Fortunately, overexpressing fatty acid binding protein ( dFabp ) increases daytime sleep and supports LTM [32].…”

Section: Resultsmentioning

confidence: 99%

Sleep Restores Behavioral Plasticity to Drosophila Mutants

et al. 2015

Self Cite

View full text Add to dashboard Cite

SUMMARY Given the role that sleep plays in modulating plasticity, we hypothesized that increasing sleep would restore memory to canonical memory mutants without specifically rescuing the causal molecular-lesion. Sleep was increased using three independent strategies: activating the dorsal Fan Shaped Body (FB), increasing the expression of Fatty acid binding protein (dFabp) or by administering the GABA-A agonist 4,5,6,7-tetrahydroisoxazolo-[5,4-c]pyridine-3-ol (THIP). Short-term memory (STM) or Long-term memory (LTM) was evaluated in rutabaga (rut) and dunce (dnc) mutants using Aversive Phototaxic Suppression (APS) and courtship conditioning. Each of the three independent strategies increased sleep and restored memory to rut and dnc mutants. Importantly, inducing sleep also reverses memory defects in a Drosophila model of Alzheimer’s disease. Together these data demonstrate that sleep plays a more fundamental role in modulating behavioral plasticity than previously appreciated and suggests that increasing sleep may benefit patients with certain neurological disorders.

show abstract

Section: Resultsmentioning

confidence: 99%

Sleep Restores Behavioral Plasticity to Drosophila Mutants

et al. 2015

Self Cite

View full text Add to dashboard Cite

show abstract

“…For example, mammalian β-defensin acts as a ligand for the melanocortin receptor 1 (Mc1r) to control melanin synthesis [25]. In Drosophila, AMPs, such as Metchnikowin (Mtk), Drosocin and Attacin, are implicated in regulation of sleep [5]; moreover, the innate immune receptor PGRP-LC is involved in homeostatic plasticity of neuromuscular junction synapse [2]. However, to our knowledge, this is the first time that AMPs made in different tissues in adult head have been found to be involved in modulating long-term associative memories.…”

Section: Normal Function Of Antimicrobial Peptides In the Adult Brainmentioning

confidence: 99%

“…Likewise, the complement system has been shown to be important for synapse formation, and immune receptors, such as Toll receptors, peptidoglycan pattern recognition receptor (PGRP), or interleukin receptors, are important for synaptic plasticity [2,3,4]. In Drosophila immune peptides have been implicated in sleep regulation [5] and nonassociative learning [6].…”

Section: Introductionmentioning

confidence: 99%

Antimicrobial peptides modulate long-term memory

Azpeleta

Weng

et al. 2018

Preprint

View full text Add to dashboard Cite

Antimicrobial peptides act as a host defense mechanism and regulate the commensal microbiome.To obtain a comprehensive view of genes contributing to long-term memory we performed mRNA sequencing from single Drosophila heads following behavioral training that produces long-lasting memory. Surprisingly, we find that two immune peptides with antimicrobial activity, Diptericin B and Gram-Negative Bacteria Binding Protein like 3, regulate long-term but not short-term memory or instinctive behavior in Drosophila. The cellular requirement of these two peptides is distinct: head fat body for DptB, and neurons for GNBP-like3. That antimicrobial peptides influence memory provides a novel example of the emerging link between the immune and nervous systems and reveals that some immune peptides may have been repurposed in the nervous system. Author summaryIt is becoming evident that the nervous system and immune system share not only some of the same molecular logic but also the same components. Here, we report a novel and unanticipated example of how immune genes influence nervous system function. During exploring how Drosophila form longlasting memories of certain experiences, we have found that antimicrobial peptides that fight bacteria in the body, are expressed in the head, and control whether an animal would form long-term memory of a food source or a mating partner. Antimicrobial peptides are detected in the brain of many species and has often been associated with dysfunction of the nervous system. This and other recent works, provide an explanation to why antimicrobial peptides may be expressed in the brain: they regulate normal functions of the brain. Both eating, and mating engage the immune system in preparation of exposure to external agents including bacteria. We speculate antimicrobial peptides were upregulated in the body to deal with immune challenges and over evolutionary time some of them are co-adopted to convey specific information about food or mating to the brain.

show abstract

“…We have previously used this approach to identify genes that convey resilience or vulnerability to sleep loss. 62 . Further, evaluating individual flies substantially reduces the computational power needed to evaluate details of behavior (path length etc.).…”

Section: Discussionmentioning

confidence: 99%

“…Determining whether a change in sleep induced by a genetic manipulation impacts these other variables is essential for understanding whether sleep has been positively or negatively impacted 26,62 . Our data clearly indicate that the increased sleep associated with impaired dopaminergic signaling is associated with impairments in spatial learning.…”

Section: Dopamine Signaling Is Required For Spatial Learningmentioning

confidence: 99%

A conserved role for sleep in supporting spatial learning in Drosophila

Melnattur

Kirszenblat

Morgan

et al. 2020

Preprint

Self Cite

View full text Add to dashboard Cite

Sleep loss and aging impair hippocampus-dependent spatial learning in mammalian systems.Here we use the fly Drosophila melanogaster to investigate the relationship between sleep and spatial learning in healthy and impaired flies. The spatial learning assay is modeled after the Morris Water Maze. The assay uses a 'thermal maze' consisting of a 5X5 grid of Peltier plates maintained at 36-37C and a visual panorama. The first trial begins when a single tile that is associated with a specific visual cue is cooled to 25°C. For subsequent trials, the cold tile is heated, the visual panorama is rotated and the flies must find the new cold-tile by remembering its association with the visual cue. Significant learning was observed with two different wild-type strains -Cs and 2U, validating our design. Sleep deprivation prior to training impaired spatial learning. Learning was also impaired in the classic learning mutant rutabaga (rut); enhancing sleep restored learning to rut mutants. Further we found that flies exhibited dramatic age-dependent cognitive decline in spatial learning starting at 20-24 days of age.These impairments could be reversed by enhancing sleep. Finally, we find that spatial learning requires dopaminergic signaling and that enhancing dopaminergic signaling in aged flies restored learning. Our results are consistent with the impairments seen in rodents and humans.These results thus demonstrate a critical conserved role for sleep in supporting spatial learning, and suggest potential avenues for therapeutic intervention during aging. STATEMENT OF SIGNIFICANCEWe have studied the relationship between sleep and plasticity using a Drosophila learning assay modified after the Morris Water Maze. Using this assay, we find that sleep loss impairs spatial learning. As in mammals, flies exhibited age-dependent spatial learning impairments.Importantly, the age-dependent impairments were reversed by enhancing sleep. Interestingly, our results mirror studies on hippocampus dependent memories in rodents and humans. Thus, our data describe an evolutionarily conserved role for sleep in regulating spatial learning. They also support augmenting sleep as a therapeutic strategy to ameliorate learning impairments.

show abstract

Differential activation of immune factors in neurons and glia contribute to individual differences in resilience/vulnerability to sleep disruption

Cited by 45 publications

References 48 publications

Sleep Restores Behavioral Plasticity to Drosophila Mutants

Sleep Restores Behavioral Plasticity to Drosophila Mutants

Antimicrobial peptides modulate long-term memory

A conserved role for sleep in supporting spatial learning in Drosophila

Contact Info

Product

Resources

About