Circadian Structural Plasticity Drives Remodeling of E Cell Output

DUHART, JOSÉ M.; HERRERO, ANASTASIA; DE LA CRUZ, GABRIEL; ISPIZUA, JUAN I.; PÍREZ, NICOLÁS; CERIANI, M. FERNANDA

CURRENT BIOLOGY

CELL PRESS

Año: 2020 vol. 30 p. 5040 - 5048

0960-9822

Behavioral outputs arise as a result of highly regulated yet flexible communication among neurons. The Drosophila circadian network includes 150 neurons that dictate the temporal organization of locomotor activity; under light-dark (LD) conditions, flies display a robust bimodal pattern. The pigment-dispersing factor (PDF)-positive small ventral lateral neurons (sLNv) have been linked to the generation of the morning activity peak (the ?M cells?), whereas the Cryptochrome (CRY)-positive dorsal lateral neurons (LNds) and the PDF-negative sLNv are necessary for the evening activity peak (the ?E cells?) [1, 2]. While each group directly controls locomotor output pathways [3], an interplay between them along with a third dorsal cluster (the DN1ps) is necessary for the correct timing of each peak and for adjusting behavior to changes in the environment [4?7]. M cells set the phase of roughly half of the circadian neurons (including the E cells) through PDF [5, 8?10]. Here, we show the existence of synaptic input provided by the evening oscillator onto the M cells. Both structural and functional approaches revealed that E-to-M cell connectivity changes across the day, with higher excitatory input taking place before the day-to-night transition. We identified two different neurotransmitters, acetylcholine and glutamate, released by E cells that are relevant for robust circadian output. Indeed, we show that acetylcholine is responsible for the excitatory input from E cells to M cells, which show preferential responsiveness to acetylcholine during the evening. Our findings provide evidence of an excitatory feedback between circadian clusters and unveil an important plastic remodeling of the E cells? synaptic connections.