Fast Feedback Inhibitory Transmission Among Circadian Clocks Keeps the Network in Tune.

FRENKEL, L; MURARO, NI; CERIANI MF

Mar del Plata, 27 Septiembre al 1 Octubre 2015.

Congreso; XXX Congreso anual de la SAN; 2015

Sociedad Argentina de Investigaciones en Neurociencias

The circadian network in the adult Drosophila brain relies on 150 neurons organized in clusters. One of them, the small lateral neurons ventral (sLNvs), is a major pacemaker since it defines the temporal organization of locomotor activity. Nevertheless, all independent yet interconnected oscillators operate coherently to provide flexibility to the network. The small and large LNvs release the PDF neuropeptide. While the relevance of PDF in the synchronization of the circadian network is well established, the role of fast neurotransmission has only recently been addressed. We showed that LNvs release glycine onto other circadian clusters and postulated that it organizes the firing pattern of clock neurons. Reducing glycine availability within LNvs alters PDF release, and remodeling of the sLNv terminals, suggesting that LNvs are also glycinergic targets. RNAi-based downregulation of a glycine receptor subunit reduced the consolidation of diurnal activity and increased nocturnal activity, decreasing overall rhythmicity. Moreover, glycine application abrogates firing of both s- and l-LNVs, consistent with an inhibition mediated by a ligand-gated Cl- channel. Furthermore, an antibody human glycine alpha1 receptor (GlyR) stained both s- and l-LNvs neurons, providing further support to the notion that LNvs express GlyR. We propose that glycine is a fast feedback inhibitory signal that modulates the output of the sLNvs, and thus provides coherence to the circadian network.