Presynaptic NMDARs in the Hippocampus Facilitate Transmitter Release at Theta Frequency

A rise in [Ca2+](i) provides the trigger for neurotransmitter release at neuronal boutons. We have used confocal microscopy and Ca2+ sensitive dyes to directly measure the action potential-evoked [Ca2+](i) in the boutons of Schaffer collaterals. This reveals that the trial-by-trial amplitude of the evoked Ca2+ transient is bimodally distributed. We demonstrate that large Ca2+ transients occur when presynaptic NMDA receptors are activated following transmitter release. Presynaptic NMDA receptor activation proves critical in producing facilitation of transmission at theta frequencies. Because large Ca2+ transients report transmitter release, their frequency on a trial-by-trial basis can be used to estimate the probability of release, p(r). We use this novel estimator to show that p(r) increases following the induction of long-term potentiation.