Circadian control in the timing of critical periods during Drosophila larval neuronal development

Developing neural circuits are maximally open to modification during defined critical periods (CPs).¹^,²^,³^,⁴ We previously identified a CP in the Drosophila embryo, from 17 to 19 h after egg laying (AEL), during which activity manipulation (optogenetic and/or pharmacological) permanently alters locomotor network stability.⁵^,⁶ Analysis of excitatory and inhibitory inputs to an identified motoneuron shows that CP activity manipulation preferentially enhances excitation.⁷ This effect is permanent, persisting through to third instars (5 days post manipulation). A manifestation of this effect is a marked increase in seizure recovery time (RT) in response to an electric shock. The induced seizure results in immediate paralysis, followed by uncoordinated peristalsis until the larva recovers sufficiently to move away from its original position (i.e., the seizure endpoint).⁶ Significantly, exposure to blue light (BL) during this same embryonic temporal window is similarly able to lead to an increased seizure RT, an effect that requires the presence of CRYPTOCHROME (CRY).⁸ Here, we identify a series of BL-sensitive CPs, occurring at ∼24-h intervals, from embryogenesis through larval development. Exposure to BL during these CPs increases the time taken for wandering larvae to recover from electroshock-induced seizure activity. This effect is absent when CRY or the principal clock-signaling neuropeptide-pigment-dispersing factor (PDF)-is absent. Thus, we uncover a novel role for the circadian clock during the embryonic and larval stages of Drosophila neural development.