Neural Network Interactions Modulate CRY-Dependent Photoresponses in Drosophila

Abstract

Light is one of the chief environmental cues that reset circadian clocks. In Drosophila, CRYPTOCHROME (CRY) mediates acute photic resetting of circadian clocks by promoting the degradation of TIMELESS in a cell-autonomous manner. Thus, even circadian oscillators in peripheral organs can independently perceive light in Drosophila. However, there is substantial evidence for nonautonomous mechanisms of circadian photoreception in the brain. We have previously shown that the morning (M) and evening (E) oscillators are critical light-sensing neurons that cooperate to shift the phase of circadian behavior in response to light input. We show here that light can efficiently phase delay or phase advance circadian locomotor behavior in male Drosophila even when either the M-or the E-oscillators are ablated, suggesting that behavioral phase shifts and their directionality are largely a consequence of the cell-autonomous nature of CRY-dependent photoreception. Our observation that the phase response curves of brain and peripheral oscillators are remarkably similar further supports this idea. Nevertheless, the neural network modulates circadian photoresponses. We show that the M-oscillator neurotransmitter pigment dispersing factor plays a critical role in the coordination between M-and E-oscillators after light exposure, and we uncover a potential role for a subset of dorsal neurons in the control of phase advances. Thus, neural modulation of autonomous light detection might play an important role in the plasticity of circadian behavior.

A robust and self-sustained peripheral circadian oscillator reveals differences in temperature compensation properties with central brain clocks

“…In contrast to circadian pacemaker neurons in the fly brain, peripheral circadian clocks of Drosophila are generally considered as weak or dampened circadian oscillators, due to their inability of maintaining molecular oscillations in constant conditions (e.g., (Levine et al, 2002;Stanewsky et al, 1997;Veleri et al, 2003). We were therefore surprised to observe sustained and non-dampening oscillations during constant conditions in cultured halteres of transgenic ptim-TIM-luc flies, a reporter for TIM protein expression ((Lamba et al, 2018), Figures 1A, B, S1). After initial synchronization to LD cycles, bioluminescence signals from individual pairs of halteres were measured in constant darkness and temperature (DD, 25°C) with 30 min or 1 hr time resolution.…”

Methylation deficiency disrupts biological rhythms from bacteria to humans

“…Assay for effect of the inhibition of the methyl cycle on invertebrate circadian clock. Halteres of two-to seven-day old transgenic ptim-TIM-LUC males 63 kept under 12 h : 12 h light:dark cycles (LD) at 25°C were bilaterally dry dissected. Each pair was transferred into one well of a 96 well plate (Topcount, Perkin Elmer) filled with medium containing 80% Schneider's medium (Sigma-Aldrich), 20% inactivated Fetal Bovine Serum (Capricorn Scientific, Ebsdorfergrund, Germany) and 1% PenStrep (Sigma-Aldrich).…”

Disrupted Glutamate Signaling in Drosophila Generates Locomotor Rhythms in Constant Light

“…Neurogenetic studies of the fly clock over the past 15 years have identified a set of 150 circadian neurons in the brain divided into seven major groupings, of which the PDF-positive small ventral lateral neurons (s-LNvs) have been described as representing the pacemaker . However, several laboratories, including ours, have demonstrated that manipulation of any one group of clock neurons has implications for the functioning of the others, highlighting the importance of their network organization (Dissel et al, 2014;Yao and Shafer, 2014;Yao et al, 2016;Chatterjee et al, 2018;Lamba et al, 2018;Delventhal et al, 2019;Schlichting et al, 2019). We have suggested that such organization is of paramount importance in defining the properties of the clock as we have shown that the period of the clock is an emergent property of the network and not a property of any single neuron or group (Dissel et al, 2014).…”

“…We have suggested that such organization is of paramount importance in defining the properties of the clock as we have shown that the period of the clock is an emergent property of the network and not a property of any single neuron or group (Dissel et al, 2014). This suggests that other circadian properties, among which, entrainment, might result from network interactions rather than by cell-autonomous properties of clock neurons (Lamba et al, 2018).…”