Developmental Changes in Energetic Demands Regulate the Emergence of Circadian Sleep-Wake Rhythms in Drosophila Larvae

Core Concepts

Developmental changes in energetic demands drive the consolidation of sleep and feeding behaviors into daily rhythms in Drosophila larvae.

Abstract

The article investigates how developmental changes in energetic demands regulate the emergence of circadian sleep-wake rhythms in Drosophila larvae. Key findings:

Feeding and sleep behaviors lack strong daily rhythms in early 2nd instar (L2) larvae but become consolidated into day-night patterns by the 3rd instar (L3) stage. This developmental transition is dependent on a functioning circadian clock.

Forcing L3 larvae to adopt the immature (L2) feeding pattern disrupts the development of sleep-wake rhythms and impairs the ability to form long-term memories (LTM), suggesting that energetic demands drive the consolidation of these behaviors.

The development of the neural circuit connecting the central clock (DN1a neurons) to arousal output (Dh44 neurons) is influenced by the larval nutritional environment. In low nutrient conditions, this circuit fails to form properly.

Dh44 neurons require glucose metabolic genes, but not amino acid sensing genes, to promote the onset of daily sleep-wake rhythms, indicating they act as nutrient sensors to coordinate these behaviors.

Inducing deeper sleep prematurely in L2 larvae is detrimental to development and does not improve LTM, suggesting that maintaining energy homeostasis is a key constraint on the developmental timing of sleep consolidation.

Together, these findings demonstrate that developmental changes in energetic capacity and nutritional status are critical regulators of the emergence of circadian sleep-wake rhythms and associated cognitive abilities.

Stats

Feeding rate is higher during the subjective day compared to the subjective night in L3 larvae, but not in L2 larvae or L3 clock mutants.
L3 larvae raised on a low sugar diet show a feeding pattern resembling that of L2 larvae on normal food.
L3 larvae raised on a low sugar diet or with thermogenetic activation of feeding neurons show disrupted sleep-wake rhythms and reduced long-term memory performance.

Quotes

"Together, our data suggest that changes to energetic demands in developing organisms trigger the formation of sleep-circadian circuits and behaviors."
"Our data indicate that the emergence of daily sleep-wake patterns is regulated by developmental changes in energetic capacity, and suggest that Dh44 neurons may be necessary for sensing of larval nutritional environments."

Key Insights Distilled From

Energetic Demands Regulate Sleep-Wake Rhythm Circuit Development

by Poe,A. R., Z... at www.biorxiv.org 09-22-2023

https://www.biorxiv.org/content/10.1101/2023.09.19.558472v2

Deeper Inquiries

How do developmental changes in body composition and nutrient storage capacity influence the regulation of sleep-wake rhythms?

During development, organisms undergo significant changes in body composition and nutrient storage capacity, which in turn influence the regulation of sleep-wake rhythms. In early life, young animals have conflicting needs between obtaining enough nutrients for growth and supporting sleep for proper nervous system development. This conflict results in rapid transitions between sleeping and feeding states. As development progresses, nutritional intake and storage capacity increase, allowing for the consolidation of feeding and sleep to specific times of the day. These changes in energetic demands and nutrient availability play a crucial role in the emergence of circadian sleep-wake rhythms. For example, in Drosophila larvae, sleep and feeding patterns become organized into daily rhythms as the larvae mature from the 2nd instar to the 3rd instar stage. The consolidation of sleep and feeding behaviors is essential for the development of circadian sleep patterns and the emergence of long-term memory capabilities. Therefore, developmental changes in body composition and nutrient storage capacity play a vital role in regulating sleep-wake rhythms as organisms mature.

What are the molecular mechanisms by which Dh44 neurons sense glucose levels to modulate sleep-wake circuit development?

Dh44 neurons play a crucial role in modulating sleep-wake rhythms by sensing glucose levels through specific molecular mechanisms. In Drosophila larvae, Dh44 neurons act as nutrient sensors to regulate food consumption and sleep-wake rhythms. These neurons require glucose metabolic genes, such as Glut1, Hexokinase-C, and Pyruvate kinase, to drive the development of sleep-wake circuits. Glucose sensing in Dh44 neurons is essential for the consolidation of sleep at specific times of the day. When glucose metabolic genes are knocked down in Dh44 neurons, there is a disruption in rhythmic changes in sleep duration and bout number, indicating the importance of these genes in regulating sleep-wake rhythms. Dh44 neurons likely sense glucose levels through specific receptors or signaling pathways that allow them to integrate information about the nutritional environment and modulate sleep-wake circuit development accordingly. Therefore, the molecular mechanisms by which Dh44 neurons sense glucose levels involve the activation of glucose metabolic genes that are essential for regulating sleep-wake rhythms.

Could manipulating energetic demands or nutrient sensing pathways in early development be a strategy to treat neurodevelopmental disorders associated with circadian disruptions?

Manipulating energetic demands or nutrient sensing pathways in early development could potentially be a strategy to treat neurodevelopmental disorders associated with circadian disruptions. Neurodevelopmental disorders such as ADHD and autism often present with disruptions in sleep and circadian rhythms. By targeting the pathways involved in sensing energetic demands and nutrients during early development, it may be possible to modulate the development of circadian sleep-wake rhythms and mitigate the effects of these disorders. For example, by manipulating the expression or activity of glucose metabolic genes in key neurons involved in sleep regulation, such as Dh44 neurons, it may be possible to restore normal sleep patterns and improve circadian rhythms in individuals with neurodevelopmental disorders. Additionally, by understanding how nutrient sensing pathways influence the development of sleep-wake circuits, targeted interventions could be designed to correct circadian disruptions and improve overall neurological function in individuals with these disorders. Further research into the specific mechanisms by which energetic demands and nutrient sensing pathways impact circadian rhythms could provide valuable insights for developing novel therapeutic approaches for neurodevelopmental disorders.