The Drosophila Circadian Clock Is a Variably Coupled Network of Multiple Peptidergic Units

Abstract

Daily rhythms in behavior emerge from networks of neurons that express molecular clocks. Drosophila’s clock neuron network consists of a diversity of cell types, yet is modeled as two hierarchically organized groups, one of which serves as a master pacemaker. Here we establish that the fly’s clock neuron network consists of multiple units of independent neuronal oscillators, each unified by its neuropeptide transmitter and mode of coupling to other units. Our work reveals that the circadian clock neuron network is not orchestrated by a small group of master pacemakers but rather consists of multiple independent oscillators, each of which drives rhythms in activity.

Circadian and feeding cues integrate to drive rhythms of physiology in Drosophila insulin-producing cells

“…The small LN v s (sLN v s) appear to be the master circadian regulators Roberts et al 2015) and coordinate the activity of the other neurons in the clock network via the release of pigment-dispersing factor (PDF), an LN V -specific neuropeptide . Although LN v s are sufficient to drive rest:activity rhythms in constant darkness (DD) and set the period of the clock, robust behavioral and physiological rhythms are an emergent property of the clock network as a whole (Peng et al 2003;Guo et al 2014;Yao and Shafer 2014;Roberts et al 2015;Liang et al 2016). LN d s and DN1 neurons are targets of PDF and play roles in regulating multiple features of circadian behavior, including rhythm strength, phase, and circadian period (Murad et al 2007;Lear et al 2009;Zhang et al 2010;Guo et al 2014).…”

Control of Sleep-Wake Cycles in Drosophila

“…The behavioral period would thus depend on the interactions between differently paced oscillators whose endogenous period and influence in the network vary according to environmental conditions. However, speed changes in all clock neurons excluding the PDF cells fell short of altering the behavioral period (Yao and Shafer 2014), in fact bolstering the older idea that PDF oscillators are the predominant determinant of the behavior period in DD. In absence of PDF signaling, the output from the s-LNvs was compromised, thereby allowing secondary oscillators to strongly influence the behavior period (Yao and Shafer 2014).…”

“…Recently, however, the existence of a centralized monopolar circuit organization in DD has been seriously challenged. The PDF clock has been shown to coherently change behavioral period only over a limited range, which is distributed asymmetrically around the 24-h focal point (Yao and Shafer 2014;Beckwith and Ceriani 2015). When the PDF neurons were forced to run at a pace beyond this specified range, multiple peaks of behavioral period emerged within a single fly, likely as a result of internal desynchronization among multiple oscillators (Yao and Shafer 2014;Beckwith and Ceriani 2015).…”

“…The PDF clock has been shown to coherently change behavioral period only over a limited range, which is distributed asymmetrically around the 24-h focal point (Yao and Shafer 2014;Beckwith and Ceriani 2015). When the PDF neurons were forced to run at a pace beyond this specified range, multiple peaks of behavioral period emerged within a single fly, likely as a result of internal desynchronization among multiple oscillators (Yao and Shafer 2014;Beckwith and Ceriani 2015). Because these oscillators are coupled to the PDF clock with differing strength and range of entrainment, they are differentially affected by speed changes in the PDF clock (Yao and Shafer 2014).…”

“…When the PDF neurons were forced to run at a pace beyond this specified range, multiple peaks of behavioral period emerged within a single fly, likely as a result of internal desynchronization among multiple oscillators (Yao and Shafer 2014;Beckwith and Ceriani 2015). Because these oscillators are coupled to the PDF clock with differing strength and range of entrainment, they are differentially affected by speed changes in the PDF clock (Yao and Shafer 2014). Thus, the behavioral period in DD is determined by the pace of not only the s-LNv clock but also by other oscillators enjoying different degrees of independence, although they were formerly thought to uniformly behave as slaves of the s-LNv pacemaker.…”