Major
Neuroscience
Anticipated Graduation Year
2020
Access Type
Restricted Access
Abstract
Most living organisms have an endogenous circadian clock, which produces 24-hr oscillations in behavioral and physiological processes. The circadian system is composed of central clock neurons that receive environmental cues, such as light and temperature, from input cells. These core clock neurons then communicate with output cells in order to produce rhythmic behaviors. An understanding of the manner through which the circadian system enacts behavioral rhythms therefore requires the identification of the cells and molecules that make up the output pathways. To that end, we recently characterized the Drosophila pars intercerebralis (PI), a functional homolog of the mammalian hypothalamus, as a major circadian output center that lies downstream of central clock neurons.1 Two populations of cells within the PI that have proved to be vital to rest:activity rhythms are Diuretic Hormone 44 (DH44) neurons and SIFamide (SIFa) neurons. Previous work has shown that the ablation of these cells results in the degradation of rest:activity rhythms1. To identify which genes within these cells are essential for normal rhythmic behavior, we conducted single-cell RNA sequencing, and used cell-specific RNA interference (RNAi) to knock down expression of candidate genes. Here, we demonstrate that knockdown of the slowpoke (slo) potassium channel or the sleepless (sss) ion channel regulatory subunit in PI neurons reliably decreases circadian rhythm strength, and hypothesize that these genes influence rest:activity rhythms in part by regulating excitability of key circadian output neurons.
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Identification of Circadian Output Genes That Affect Rest:Activity Rhythms in Drosophila
Most living organisms have an endogenous circadian clock, which produces 24-hr oscillations in behavioral and physiological processes. The circadian system is composed of central clock neurons that receive environmental cues, such as light and temperature, from input cells. These core clock neurons then communicate with output cells in order to produce rhythmic behaviors. An understanding of the manner through which the circadian system enacts behavioral rhythms therefore requires the identification of the cells and molecules that make up the output pathways. To that end, we recently characterized the Drosophila pars intercerebralis (PI), a functional homolog of the mammalian hypothalamus, as a major circadian output center that lies downstream of central clock neurons.1 Two populations of cells within the PI that have proved to be vital to rest:activity rhythms are Diuretic Hormone 44 (DH44) neurons and SIFamide (SIFa) neurons. Previous work has shown that the ablation of these cells results in the degradation of rest:activity rhythms1. To identify which genes within these cells are essential for normal rhythmic behavior, we conducted single-cell RNA sequencing, and used cell-specific RNA interference (RNAi) to knock down expression of candidate genes. Here, we demonstrate that knockdown of the slowpoke (slo) potassium channel or the sleepless (sss) ion channel regulatory subunit in PI neurons reliably decreases circadian rhythm strength, and hypothesize that these genes influence rest:activity rhythms in part by regulating excitability of key circadian output neurons.