Synapse independence breaks down during highly synchronous network activity in the rat hippocampus

The discharge pattern of hippocampal pyramidal cells (PC) varies depending on the behaviour of the animal and on the accompanying network states. During theta activity, PCs fire asynchronously at low rates whereas during sharp waves PCs increase their firing frequency and many cells fire synchronously. In the present study, we addressed how the presynaptic activity of CA1 PCs influences the precise operation of their output synapses. Asynchronous presynaptic discharge was mimicked by activating only a single PC during paired recordings, whereas the highly synchronous presynaptic firing was emulated by extracellularly stimulating the axons of ≈ 70 PCs in acute hippocampal slices. By using low‐ and high‐affinity glutamate receptor competitive antagonists to monitor the synaptic glutamate concentration transient, we show that the synaptic transmitter concentration varies depending on the release probability ( P r ) when many fibres are synchronously activated. Our kinetic analysis revealed that an ≈ 5‐fold increase in P r from the beginning to the end of an action potential train resulted in a slowing down of the decay of evoked EPSCs, suggesting neurotransmitter spillover between neighbouring synapses. In agreement with this prediction, the slowing of the decay was reversed by the application of the low‐affinity antagonist γ‐D‐glutamyl‐glycine. In contrast, altering P r had no effect on the kinetics of unitary EPSCs. Our data demonstrate that synapse independence breaks down during synchronous presynaptic activity, but the point‐to‐point communication is preserved when PCs fire asynchronously.