Summary: Fruit flies with genetic mutations that severely reduce sleep show enhanced performance in olfactory memory tasks, challenging assumptions about sleep’s role in cognition. This paradox appears to be driven by increased protein kinase A (PKA) signaling in the mushroom body, a brain region responsible for memory and sleep regulation.
The study suggests that heightened memory performance may come at the cost of sleep and lifespan, hinting at a deeper evolutionary trade-off. Researchers also draw potential links to autism, as the molecular pathways involved in these fruit fly mutants resemble mechanisms tied to neurodevelopmental disorders in humans.
Key Facts:
- Enhanced memory in sleep mutants: Fruit flies with sleep deficits outperform controls in memory tasks.
- PKA signaling role: Elevated PKA activity mediates both memory enhancement and sleep suppression.
- Autism connection: Mutations in the same pathway are linked to traits seen in autism spectrum disorder.
Source: PLOS
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.”
About this sleep and memory research news
Author: Claire Turner
Source: PLOS
Contact: Claire Turner – PLOS
Image: The image is credited to Neuroscience News
Original Research: Open access.
“Enhanced memory despite severe sleep loss in Drosophila insomniac mutants” by Stephan Sigrist et al. PLOS Biology
Abstract
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 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.
