Postsynaptic depolarisation enhances transmitter release and causes the appearance of responses at "silent" synapses in rat hippocampus.
Recent data indicate that most "silent" synapses in the hippocampus are "presynaptically silent" due to low transmitter release rather than "postsynaptically silent" due to "latent" receptors of alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid type (AMPARs). That synapses bearing only N-methyl-d-aspartate (NMDAR) receptors do exist is suggested by the decreased number of transmission failures during postsynaptic depolarisation and by the presence of NMDA-mediated excitatory postsynaptic currents (EPSCs) in synapses silent at rest. We tested whether these effects could be due to potentiated transmitter release at depolarised postsynaptic potentials rather than removal of Mg(2+) block from NMDARs. Using whole-cell recordings of minimal EPSCs from CA1 and CA3 neurones of hippocampal slices we confirmed decreased incidence of failures at +40 mV as compared with -60 mV. This effect was associated with a gradual increase of EPSC amplitude after switching to +40 mV and with a decrease of paired-pulse facilitation. In initially silent synapses, potentiation of pharmacologically isolated AMPAR-mediated EPSCs was still observed at +40 mV and this persisted after stepping back to -60 mV. All above effects were blocked when the cell was dialysed with the Ca(2+) chelator BAPTA (20 mM). These observations are difficult to reconcile with the "latent AMPAR" hypothesis and suggest an alternative explanation, namely that the reduction in failure rates at positive potentials is due to potentiation of transmitter release following Ca(2+) influx through NMDARs. Our results suggest that silent synapses can be mainly "presynaptically" rather than "postsynaptically silent" and thus increased transmitter release rather than insertion of AMPARs is a major mechanism of early long-term potentiation maintenance.
Voronin
L L
LL
Institute of Higher Nervous Activity and Neurophysiology, Russian Academy of Sciences, Butlerova 5a, 117485 Moscow, Russia.
Altinbaev
R S
RS
Bayazitov
I T
IT
Gasparini
S
S
Kasyanov
A V
AV
Saviane
C
C
Savtchenko
L
L
Cherubini
E
E
D000818:Animals; D002118:Calcium / Q000378:metabolism; D019706:Excitatory Postsynaptic Potentials / Q000502:physiology*; D006624:Hippocampus / Q000502:physiology*; D008564:Membrane Potentials / Q000502:physiology; D051381:Rats; D017208:Rats, Wistar; D018091:Receptors, AMPA / Q000502:physiology; D016194:Receptors, N-Methyl-D-Aspartate / Q000502:physiology; D013569:Synapses / Q000502:physiology*; D009435:Synaptic Transmission / Q000502:physiology
D018091:Receptors, AMPA; D016194:Receptors, N-Methyl-D-Aspartate; D002118:Calcium