Neuronal circuitry controlling circadian photoreception in Drosophila

Abstract

Circadian clocks are endogenous timekeeping mechanisms, which give the sense of time-of-day to most organisms. To help the organisms to adapt to daily fluctuations in the environment, circadian clocks are reset by various environmental cues. Light is one of the cardinal environmental cues that synchronize circadian clocks. In a standard 12:12 light-dark condition, Drosophila exhibits bimodal activity pattern in the anticipation of lights-on and -off. The morning peak of activity is generated by Pigment Dispersing Factor (PDF) positive small ventro-lateral neurons (sLNvs) called the M-oscillators, while the evening peak of activity is generated by the dorsolateral neurons (LNds) and the 5th sLNv together referred to as the E-oscillators. Since the Drosophila circadian clock is extremely sensitive to light, a brief light exposure can robustly shift the phase of circadian behavior. The model for this resetting posits that circadian photoreception is cell-autonomous: the photoreceptor CRYPTOCHROME (CRY) senses light, binds to TIMELESS (TIM) and promotes its degradation via JETLAG (JET). However, it was more recently proposed that interactions between circadian neurons are also required for phase resetting. The goal of my thesis was to map the neuronal circuitry controlling circadian photoreception in Drosophila. In the first half of my dissertation (Chapter II), using a novel severe jetset mutant and JET RNAi, we identified M- and E-oscillators as critical light sensing neurons. We also found that JET functions cell-autonomously to promote TIM degradation in M- and E-oscillators, and non-autonomously in E-oscillators when expressed in M-oscillators. However, JET expression was required in both groups of neurons to phase-shift locomotor rhythms in response to light input. Thus M- and E-oscillators cooperate to shift circadian behavior in response to photic cues. In chapter III, unexpectedly, we found that light can delay or advance circadian behavior even when the M- or E-oscillators are genetically ablated or incapacitated suggesting that behavioral phase shifts in response to light are largely a consequence of cell autonomous light detection by CRY and governed by the molecular properties of the pacemaker. Nevertheless, neural interactions are integral in modulating light responses. The M-oscillator neurotransmitter, PDF was important in coordinating M- and E-oscillators for circadian behavioral response to light input. Moreover, we uncover a potential role for a subset of Dorsal neurons in control of phase advances specifically. Hence, neural modulation of cell autonomous light detection contributes to plasticity of circadian behavior and facilitates its adaptation to environmental inputs.