TY - JOUR
T1 - Dual Ca2+ modulation of glycinergic synaptic currents in rodent hypoglossal motoneurones
AU - Mukhtarov, Marat
AU - Ragozzino, Davide
AU - Bregestovski, Piotr
PY - 2005/12/15
Y1 - 2005/12/15
N2 - 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.
AB - 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.
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U2 - 10.1113/jphysiol.2005.094862
DO - 10.1113/jphysiol.2005.094862
M3 - Article
C2 - 16123105
AN - SCOPUS:29244431645
VL - 569
SP - 817
EP - 831
JO - Journal of Physiology
JF - Journal of Physiology
SN - 0022-3751
IS - 3
ER -