Enhanced memory despite severe sleep loss in Drosophila insomniac mutants.

Sleep is crucial for cognitive functions and life span across species. While sleep homeostasis and cognitive processes are linked through cellular and synaptic plasticity, the signaling pathways connecting them remain unclear. Here, we show that Drosophila insomniac (inc) short sleep mutants, which...

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Main Authors: Sheng Huang, Chengji Piao, Zhiying Zhao, Christine B Beuschel, Oriane Turrel, David Toppe, Stephan J Sigrist
Format: Article
Language:English
Published: Public Library of Science (PLoS) 2025-03-01
Series:PLoS Biology
Online Access:https://doi.org/10.1371/journal.pbio.3003076
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author Sheng Huang
Chengji Piao
Zhiying Zhao
Christine B Beuschel
Oriane Turrel
David Toppe
Stephan J Sigrist
author_facet Sheng Huang
Chengji Piao
Zhiying Zhao
Christine B Beuschel
Oriane Turrel
David Toppe
Stephan J Sigrist
author_sort Sheng Huang
collection DOAJ
description Sleep is crucial for cognitive functions and life span across species. While sleep homeostasis and cognitive processes are linked through cellular and synaptic plasticity, the signaling pathways connecting them remain unclear. Here, we show that Drosophila insomniac (inc) short sleep mutants, which lack an adaptor protein for the autism-associated Cullin-3 ubiquitin ligase, exhibited enhanced Pavlovian aversive olfactory learning and memory, unlike other sleep mutants with normal or reduced memory. Through a genetic modifier screen, we found that a mild reduction of Protein Kinase A (PKA) signaling specifically rescued the sleep and longevity phenotypes of inc mutants. However, this reduction further increased their excessive memory and mushroom body overgrowth. Since inc mutants displayed higher PKA signaling, we propose that inc loss-of-function suppresses sleep via increased PKA activity, which also constrains the excessive memory of inc mutants. Our data identify a signaling cascade for balancing sleep and memory functions, and provide a plausible explanation for the sleep phenotypes of inc mutants, suggesting that memory hyperfunction can provoke sleep deficits.
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institution Kabale University
issn 1544-9173
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language English
publishDate 2025-03-01
publisher Public Library of Science (PLoS)
record_format Article
series PLoS Biology
spelling doaj-art-8c3e4742f3314ff794987e8e82aa28602025-08-20T03:25:20ZengPublic Library of Science (PLoS)PLoS Biology1544-91731545-78852025-03-01233e300307610.1371/journal.pbio.3003076Enhanced memory despite severe sleep loss in Drosophila insomniac mutants.Sheng HuangChengji PiaoZhiying ZhaoChristine B BeuschelOriane TurrelDavid ToppeStephan J SigristSleep is crucial for cognitive functions and life span across species. While sleep homeostasis and cognitive processes are linked through cellular and synaptic plasticity, the signaling pathways connecting them remain unclear. Here, we show that Drosophila insomniac (inc) short sleep mutants, which lack an adaptor protein for the autism-associated Cullin-3 ubiquitin ligase, exhibited enhanced Pavlovian aversive olfactory learning and memory, unlike other sleep mutants with normal or reduced memory. Through a genetic modifier screen, we found that a mild reduction of Protein Kinase A (PKA) signaling specifically rescued the sleep and longevity phenotypes of inc mutants. However, this reduction further increased their excessive memory and mushroom body overgrowth. Since inc mutants displayed higher PKA signaling, we propose that inc loss-of-function suppresses sleep via increased PKA activity, which also constrains the excessive memory of inc mutants. Our data identify a signaling cascade for balancing sleep and memory functions, and provide a plausible explanation for the sleep phenotypes of inc mutants, suggesting that memory hyperfunction can provoke sleep deficits.https://doi.org/10.1371/journal.pbio.3003076
spellingShingle Sheng Huang
Chengji Piao
Zhiying Zhao
Christine B Beuschel
Oriane Turrel
David Toppe
Stephan J Sigrist
Enhanced memory despite severe sleep loss in Drosophila insomniac mutants.
PLoS Biology
title Enhanced memory despite severe sleep loss in Drosophila insomniac mutants.
title_full Enhanced memory despite severe sleep loss in Drosophila insomniac mutants.
title_fullStr Enhanced memory despite severe sleep loss in Drosophila insomniac mutants.
title_full_unstemmed Enhanced memory despite severe sleep loss in Drosophila insomniac mutants.
title_short Enhanced memory despite severe sleep loss in Drosophila insomniac mutants.
title_sort enhanced memory despite severe sleep loss in drosophila insomniac mutants
url https://doi.org/10.1371/journal.pbio.3003076
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