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Insomniac fruit fly mutants show enhanced memory despite severe sleep loss

A signaling pathway in insomniac mutants rebalances sleep and memory functions

Insomniac fruit fly mutants show enhanced memory despite severe sleep loss
2025-03-20
(Press-News.org) Fruit fly mutants that have severe sleep deficits perform better at olfactory learning and memory tasks, according to a study published March 20th in the open-access journal PLOS Biology by Sheng Huang and Stephan Sigrist from Freie Universität Berlin, Germany, and colleagues. The paradox of enhanced memory despite sleep loss could be explained by protein kinase A (PKA) signaling in the mushroom body of the fly brain. 

Sleep is a dynamic process conserved from invertebrates to mammals and humans. Although sleep is thought to serve many purposes, it is often studied for its restorative roles, which are believed to optimize lifespan and cognition. The fruit fly Drosophila melanogaster has long been used to study associative learning and memory. The mushroom body in the fly brain plays essential roles in both memory and sleep regulation. Yet it remains unclear how signaling in the fly mushroom body controls the balance between memory function and sleep levels.

In the new study, Huang, Sigrist, and colleagues examined this question using Drosophila insomniac (inc) short sleep mutants. The inc mutants showed robustly increased performance in olfactory learning and memory, despite their severe sleep deficits. A screen for genetic modifiers revealed that the PKA signaling pathway specifically mediates the sleep deficits of inc mutants. Elevated PKA signaling also contributes to the shorter life expectancy of inc mutants. However, a reduction of PKA signaling further increased their excessive memory and mushroom body overgrowth.

Since inc mutants displayed higher PKA signaling, the researchers propose that this mutation in the inc gene suppresses sleep via increased PKA activity in the mushroom body, which also constrains the excessive memory of inc mutants. While this elevated PKA signaling restricts excessive memory, it comes at the cost of reduced sleep levels and shortened lifespan in inc mutants. According to the authors, the findings reveal a signaling cascade for balancing sleep and memory functions, and provide a plausible explanation for the sleep patterns of inc mutants, suggesting that enhanced memory can provoke sleep deficits.

Interestingly, behavioral hyperfunction, coupled with sleep deficits and cognitive imbalances, mirrors hallmark traits of neurodevelopmental disorders such as autism. As Inc functions as an adaptor protein for Cullin-3 ubiquitin ligase, and Cullin-3 mutations have been associated with autism spectrum disorder, the findings provide a potential mechanistic connection between neurodevelopmental hyperfunction and the origins of autism.

The authors add, “Enhanced memory resulting from developmental neural circuit overgrowth: autism-related Drosophila insomniac mutants promote PKA signaling to suppress their excessive memory function, and consequently trigger severe sleep loss.”

 

In your coverage, please use this URL to provide access to the freely available paper in PLOS Biology: https://plos.io/4itdoIB  

Citation: Huang S, Piao C, Zhao Z, Beuschel CB, Turrel O, Toppe D, et al. (2025) Enhanced memory despite severe sleep loss in Drosophila insomniac mutants. PLoS Biol 23(3): e3003076. https://doi.org/10.1371/journal.pbio.3003076

Author countries: Germany

Funding: see manuscript

END

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Insomniac fruit fly mutants show enhanced memory despite severe sleep loss

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[Press-News.org] Insomniac fruit fly mutants show enhanced memory despite severe sleep loss
A signaling pathway in insomniac mutants rebalances sleep and memory functions