Lessons From Sleeping Flies: Insights fromDrosophila melanogasteron the Neuronal Circuitry and Importance of Sleep

Abstract

Sleep is a highly conserved behavior whose role is as yet unknown, although it is widely acknowledged as being important. Here we provide an overview of many vital questions regarding this behavior, that have been addressed in recent years using the genetically tractable model organism Drosophila melanogaster in several laboratories around the world. Rest in D. melanogaster has been compared to mammalian sleep and its homeostatic and circadian regulation have been shown to be controlled by intricate neuronal circuitry involving circadian clock neurons, mushroom bodies, and pars intercerebralis, although their exact roles are not entirely clear. We draw attention to the yet unanswered questions and contradictions regarding the nature of the interactions between the brain regions implicated in the control of sleep. Dopamine, octopamine, γ-aminobutyric acid (GABA), and serotonin are the chief neurotransmitters identified as functioning in different limbs of this circuit, either promoting arousal or sleep by modulating membrane excitability of underlying neurons. Some studies have suggested that certain brain areas may contribute towards both sleep and arousal depending on activation of specific subsets of neurons. Signaling pathways implicated in the sleep circuit include cyclic adenosine monophosphate (cAMP) and epidermal growth factor receptor-extracellular signal-regulated kinase (EGFR-ERK) signaling pathways that operate on different neural substrates. Thus, this field of research appears to be on the cusp of many new and exciting findings that may eventually help in understanding how this complex physiological phenomenon is modulated by various neuronal circuits in the brain. Finally, some efforts to approach the "Holy Grail" of why we sleep have been summarized.

Identification of a genetic network for an ecologically relevant behavioural phenotype in Drosophila melanogaster

“…The phenotypic effects on pupation height of four randomly selected genes from the predicted network were further experimentally confirmed (Table 3). These include another well-studied gene Egfr, which is the transmembrane tyrosine kinase receptor for signalling ligands in the TGFα family and was also found to function in neuronal development and behavioural traits in Drosophila (King, Eddison, Kaun, & Heberlein, 2014;Potdar & Sheeba, 2013). Ras85D encodes a protein that acts downstream of several cell signals, most notably of receptor tyrosine kinases (RTKs), and has been reported to be involved in pupal size determination (Li, Li, Jin, Chen, & Ma, 2017).…”

Reorganization of Sleep by Temperature in Drosophila Requires Light, the Homeostat, and the Circadian Clock

“…As in mammals, sleep in Drosophila is associated with reduced sensory responsiveness, is under circadian and homeostatic regulation [7, 8], and is associated with altered oscillatory brain activity [9–11]. Researchers have identified a number of genes [12], circuits [13], and biological processes [14, 15] that regulate fly sleep. However, the mechanisms underlying the regulation of Drosophila sleep by temperature have not been extensively investigated.…”

Analysis of genes within the schizophrenia-linked 22q11.2 deletion identifies interaction of night owl/LZTR1 and NF1 in GABAergic sleep control

“…Furthermore, GABAergic innervation has been shown to regulate "clock" neurons expressing the Pigment Dispersing Factor (PDF) peptide, comprising a limited number of wakepromoting neurons, the small and large ventral lateral neurons (s-LNv and l-LNv, respectively) [40,41]. To assess the function of nowl in these neurons, the Pdf-GAL4 (Pdf>) driver was used to drive expression in all PDF-expressing neurons, while the dimm-GAL4 (dimm>) driver allowed for knockdown in peptidergic neurosecretory cells including the l-LNvs, suggested to be the only sleep-regulatory neurons in this subset of cells [42].…”