Dual Ca2+ modulation of glycinergic synaptic currents in rodent hypoglossal motoneurones

Marat Mukhtarov, Davide Ragozzino, Piotr Bregestovski

Research output: Contribution to journalArticlepeer-review

Abstract

Glycinergic synapses are implicated in the coordination of reflex responses, sensory signal processing and pain sensation. Their activity is pre- and postsynaptically regulated, although mechanisms are poorly understood. Using patch-damp recording and Ca2+ imaging in hypoglossal motoneurones from rat and mouse brainstem slices, we address here the role of cytoplasmic Ca2+ (Cai) in glycinergic synapse modulation. Ca2+ influx through voltage-gated or NMDA receptor channels caused powerful transient inhibition of glycinergic IPSCs. This effect was accompanied by an increase in both the failure rate and paired-pulse ratio, as well as a decrease in the frequency of mIPSCs, suggesting a presynaptic mechanism of depression. Inhibition was reduced by the cannabinoid receptor antagonist SR141716A and occluded by the agonist WIN55,212-2, indicating involvement of endocannabinoid retrograde signalling. Conversely, in the presence of SR141716A, glycinergic IPSCs were potentiated postsynaptically by glutamate or NMDA, displaying a Ca2+-dependent increase in amplitude and decay prolongation. Both presynaptic inhibition and postsynaptic potentiation were completely prevented by strong Cai buffering (20 mm BAPTA). Our findings demonstrate two independent mechanisms by which Ca2+ modulates glycinergic synaptic transmission: (i) presynaptic inhibition of glycine release and (ii) postsynaptic potentiation of GlyR-mediated responses. This dual Ca2+-induced regulation might be important for feedback control of neurotransmission in a variety of glycinergic networks in mammalian nervous systems.

Original languageEnglish
Pages (from-to)817-831
Number of pages15
JournalJournal of Physiology
Volume569
Issue number3
DOIs
Publication statusPublished - Dec 15 2005

ASJC Scopus subject areas

  • Physiology

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