Circadian Structural Plasticity Drives Remodeling of E Cell Output

• Published in: Current biology Vol. 30; no. 24; pp. 5040 - 5048.e5
• Main Authors: Duhart, José M., Herrero, Anastasia, de la Cruz, Gabriel, Ispizua, Juan I., Pírez, Nicolás, Ceriani, M. Fernanda
• Format: Journal Article
• Language: English
• Published: England Elsevier Inc 21.12.2020
• Subjects: acetylcholine; circadian network; circadian structural remodeling; E oscillator; fast neurotransmission; glutamate; M oscillator; synaptic GRASP; time-of-day-dependent postsynaptic response; trans-Tango; E oscillator; circadian network; time-of-day-dependent postsynaptic response; synaptic GRASP; fast neurotransmission; circadian structural remodeling; M oscillator; acetylcholine; trans-Tango; glutamate
• ISSN: 0960-9822; 1879-0445
• DOI: 10.1016/j.cub.2020.09.057

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. [Display omitted] •E cells exhibit structural remodeling of their presynaptic terminals across the day•E cells release two neurotransmitters, acetylcholine and glutamate•Activation of E cells depolarizes M cells preferentially during late day•Hindering neurotransmission in E cells impairs clock outputs In nature, Drosophila organizes its activity around dawn and dusk, relying on its clock. Clock neurons undergo structural remodeling, and hence, their synaptic connections change daily. Duhart et al. demonstrate that circadian remodeling fine-tunes the communication between clock clusters and thus modulates their output to the circadian network.