Large Ventral Lateral Neurons Determine the Phase of Evening Activity Peak across Photoperiods in Drosophila melanogaster

Abstract

The dual-oscillator model, originally proposed as a mechanism for how vertebrates adapt to seasonal changes, has been invoked to explain circadian entrainment in Drosophila melanogaster. Distinct subsets of neurons have been designated as "morning" and "evening" oscillators that function as regulators of rhythmic activity/rest behavior. Some studies have led to a model in which a subset of 8 "morning" cells (4 bilaterally located small ventral lateral neurons) and another subset of approximately 130 "evening" cells exert different levels of dominance within the circadian circuit in different seasons. However, many studies propose a more integrative neuronal network, with the whole network orchestrating activity/rest rhythms in different seasons, as opposed to hierarchical dominance among neurons. Within the circadian network, our understanding of the role of the large ventral lateral neurons (l-LN(v)) has thus far been limited to conveying light information to the clocks and as light-activated neurons mediating arousal. In support of the framework of a more distributed model, we report an important circadian clock-related role for the l-LN(v) in electrical activity-dependent phasing of the evening peak across a range of photoperiods. Further, we propose a model in which l-LN(v) enable adaptation to seasonal changes by regulating the phase of the evening peak. Additionally, we demonstrate a hitherto unknown role for the small ventral lateral neurons (s-LN(v)) in the arousal circuit, thus showing that neuronal function is flexible such that certain neurons can play more than one role in distinct circuits.

The Logic of Circadian Organization in Drosophila

“…Considering all results reported above, we favor a model based on a flexible network of circadian neurons, which operates under any environmental condition. Our model complements and extends evidence by others of network organization as opposed to hierarchical dominance among neurons under LD and DD conditions [ 34–36 ].…”

Neuroanatomical details of the lateral neurons of Drosophila melanogaster support their functional role in the circadian system

“…The classification of the l‐LN v s as M‐oscillators is a controversely discussed fact (e.g., Beuchle, Jaumouille, & Nagoshi, ; Abruzzi, Chen, Nagoshi, Zadina, & Rosbash, ). Though, the release of high levels of PDF which acts directly on E‐cells to control the phasing of the evening activity peak independently from s‐LN v signaling (Cusumano et al, ; Potdar & Sheeba, ; Schlichting et al, ), as well as the described role of l‐LN v s in the control of sleep and arousal (Parisky et al, ; Sheeba, Gu, Sharma, O'Dowd, & Holmes, ; Gmeiner et al, ) justifies this assumption.…”

Aging and the clock: Perspective from flies to humans

“…Genetic strategies to enhance the output signaling activity of specific circadian neuron groups have also been employed to counter age‐induced declines. In the Drosophila central brain circadian system, the small ventral lateral neurons provide signaling for the morning oscillator (Grima, Chélot, Xia & Rouyer, ; Stoleru, Peng, Agosto & Rosbash, ) or potentially act as the main oscillator (Rieger, Shafer, Tomioka & Helfrich‐Förster, ), while the large ventral lateral neurons are generally thought to provide an arousal function as part of the circadian circuit (Parisky et al., ; Potdar & Sheeba, ; Shang, Griffith & Rosbash, ; Sheeba et al., ). When the activity of the ventral lateral neurons was manipulated in aging flies via input dopaminergic signaling, age‐dependent declines in neural structural plasticity were rescued as was activity dependent increases in sleep (Donlea, Pimentel & Miesenböck, ).…”