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Circadian Structural Plasticity Drives Remodeling of E Cell Output

2020; Elsevier BV; Volume: 30; Issue: 24 Linguagem: Inglês

10.1016/j.cub.2020.09.057

1879-0445

José M. Duhart, Anastasia Herrero, Gabriel de la Cruz, Juan Ignacio Ispizua, Nicolás Pírez, M. Fernanda Ceriani,

Light effects on plants

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") [1Stoleru D. Peng Y. Agosto J. Rosbash M. Coupled oscillators control morning and evening locomotor behaviour of Drosophila.Nature. 2004; 431: 862-868Crossref PubMed Scopus (486) Google Scholar, 2Grima B. Chélot E. Xia R. Rouyer F. Morning and evening peaks of activity rely on different clock neurons of the Drosophila brain.Nature. 2004; 431: 869-873Crossref PubMed Scopus (460) Google Scholar]. While each group directly controls locomotor output pathways [3Liang X. Ho M.C.W. Zhang Y. Li Y. Wu M.N. Holy T.E. Taghert P.H. Morning and evening circadian pacemakers independently drive premotor centers via a specific Dopamine relay.Neuron. 2019; 102: 843-857.e4Abstract Full Text Full Text PDF PubMed Scopus (30) Google Scholar], 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 [4Yao Z. Bennett A.J. Clem J.L. Shafer O.T. The Drosophila clock neuron network features diverse coupling modes and requires network-wide coherence for robust circadian rhythms.Cell Rep. 2016; 17: 2873-2881Abstract Full Text Full Text PDF PubMed Scopus (21) Google Scholar, 5Liang X. Holy T.E. Taghert P.H. A series of suppressive signals within the Drosophila circadian neural circuit generates sequential daily outputs.Neuron. 2017; 94: 1173-1189.e4Abstract Full Text Full Text PDF PubMed Scopus (62) Google Scholar, 6Guo F. Yu J. Jung H.J. Abruzzi K.C. Luo W. Griffith L.C. Rosbash M. Circadian neuron feedback controls the Drosophila sleep--activity profile.Nature. 2016; 536: 292-297Crossref PubMed Scopus (147) Google Scholar, 7Chatterjee A. Lamaze A. De J. Mena W. Chélot E. Martin B. Hardin P. Kadener S. Emery P. Rouyer F. Reconfiguration of a multi-oscillator network by light in the Drosophila circadian clock.Curr. Biol. 2018; 28: 2007-2017.e4Abstract Full Text Full Text PDF PubMed Scopus (28) Google Scholar]. M cells set the phase of roughly half of the circadian neurons (including the E cells) through PDF [5Liang X. Holy T.E. Taghert P.H. A series of suppressive signals within the Drosophila circadian neural circuit generates sequential daily outputs.Neuron. 2017; 94: 1173-1189.e4Abstract Full Text Full Text PDF PubMed Scopus (62) Google Scholar, 8Stoleru D. Peng Y. Nawathean P. Rosbash M. A resetting signal between Drosophila pacemakers synchronizes morning and evening activity.Nature. 2005; 438: 238-242Crossref PubMed Scopus (223) Google Scholar, 9Yoshii T. Wülbeck C. Sehadova H. Veleri S. Bichler D. Stanewsky R. Helfrich-Förster C. The neuropeptide pigment-dispersing factor adjusts period and phase of Drosophila's clock.J. Neurosci. 2009; 29: 2597-2610Crossref PubMed Scopus (166) Google Scholar, 10Liang X. Holy T.E. Taghert P.H. Synchronous Drosophila circadian pacemakers display nonsynchronous Ca2+ rhythms in vivo.Science. 2016; 351: 976-981Crossref PubMed Scopus (95) Google Scholar]. 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.