Glycine: a fast neurotransmitter that provides coherence to the circadian network

LIA FRENKEL; NARA I MURARO; MARIA SILVINA MARCORA; GUILLERMO BERNABÓ; CHRISTIANNE HERMANN-LUIB; EDUARDO CASTAÑO; CRISTINA MARINO BUSJLE; C HELFRICH-FÖRSTER ; MARIA FERNANDA CERIANI

Girona

Conferencia; Gordon Research Conference on Chronobiology; 2015

Gordon Research Conference on Chronobiology

The circadian network in the adult Drosophila brain relies on about 150 neurons organized in clusters and named according to their anatomical location. One of them, the small lateral neurons ventral (sLNvs), is considered a major pacemaker since it defines the temporal organization of locomotor activity under constant conditions. In recent years the relevance of specific clusters has been explored under different environmental conditions and the emergent picture reflects independent yet interconnected oscillators that provide flexibility to the underlying network. Despite the fact that sLNvs have been the focus of intense analysis, basic aspects of their physiology are still elusive. sLNvs release the neuropeptide Pigment Dispersing Factor (PDF) as well as a putative fast neurotransmitter, likely involved in synchronizing the circadian network as it was described in mammals. We pursued the identification of the classical neurotransmitter released by sLNv examining locomotor activity patterns after disrupting either membrane or vesicular neurotransmitter transporters in PDF+ neurons. RNAi-based downregulation indicated that reduced glycine transporter levels increases period length nearly an hour without affecting rhythmicity. A decrease in intracellular glycine availability likely accounts for the period lengthening phenotype, as disrupting glycine synthesis has a similar effect. Reducing glycine concomitantly alters PDF release and, in turn, alters the circadian remodeling of sLNv terminals at the dorsal protocerebrum. To map glycinergic targets distinct subunits of the putative glycine receptor were downregulated in specific subsets of circadian neurons. Overall, impairing glycinergic transmission results in deconsolidated activity patterns, underscoring a role for this neurotransmitter in defining the relative contribution of specific clusters in order to achieve a coherent output. Interestingly, silencing specific subunits in specific subsets alters behavior to a different degree, suggesting a differential receptor identity that could in turn modulate their response. Glycine application abrogates firing of clock neurons, which is consistent with the expected inhibitory effect mediated by a neurotransmitter-gated Cl- channel. Despite more work is ensured to fully understand the logic of this circadian ensemble, our results shed light on some basic principles on how such organization is encoded.