Short-term potentiation of mEPSCs requires N-, P/Q- and L-type Ca2+ channels and mitochondria in the supraoptic nucleus.
The glutamatergic synapses of the supraoptic nucleus display a unique activity-dependent plasticity characterized by a barrage of tetrodotoxin-resistant miniature EPSCs (mEPSCs) persisting for 5-20 min, causing postsynaptic excitation. We investigated how this short-term synaptic potentiation (STP) induced by a brief high-frequency stimulation (HFS) of afferents was initiated and maintained without lingering presynaptic firing, using in vitro patch-clamp recording on rat brain slices. We found that following the immediate rise in mEPSC frequency, STP decayed with two-exponential functions indicative of two discrete phases. STP depends entirely on extracellular Ca(2+) which enters the presynaptic terminals through voltage-gated Ca(2+) channels but also, to a much lesser degree, through a pathway independent of these channels or reverse mode of the plasma membrane Na(+)-Ca(2+) exchanger. Initiation of STP is largely mediated by any of the N-, P/Q- or L-type channels, and only a simultaneous application of specific blockers for all these channels attenuates STP. Furthermore, the second phase of STP is curtailed by the inhibition of mitochondrial Ca(2+) uptake or mitochondrial Na(+)-Ca(2+) exchanger. mEPSCs amplitude is also potentiated by HFS which requires extracellular Ca(2+). In conclusion, induction of mEPSC-STP is redundantly mediated by presynaptic N-, P/Q- and L-type Ca(2+) channels while the second phase depends on mitochondrial Ca(2+) sequestration and release. Since glutamate influences unique firing patterns that optimize hormone release by supraoptic magnocellular neurons, a prolonged barrage of spontaneous excitatory transmission may aid in the induction of respective firing activities.
Quinlan
Michelle E
ME
Division of BioMedical Sciences, Faculty of Medicine, Memorial University, 300 Prince Philip Drive, St John's, NL A1B 3V6, Canada.
Alberto
Christian O
CO
Hirasawa
Michiru
M
D000818:Animals; D002118:Calcium / Q000378:metabolism; D002121:Calcium Channel Blockers / Q000494:pharmacology; D015220:Calcium Channels / Q000378:metabolism*; D004594:Electrophysiology; D005071:Evoked Potentials / Q000502:physiology; D019706:Excitatory Postsynaptic Potentials / Q000502:physiology*; D008297:Male; D008928:Mitochondria / Q000378:metabolism*; D051381:Rats; D017207:Rats, Sprague-Dawley; D013495:Supraoptic Nucleus / Q000502:physiology*
D002121:Calcium Channel Blockers; D015220:Calcium Channels; D002118:Calcium