Abstract

Activity-dependent modifications of neuronal excitability are of key functional importance because they accomplish general postsynaptic control of the flow of synaptic signals. We tested the modifications of synaptic efficacy evoked in rat CA1 hippocampal pyramidal neurons during the short- term activity-dependent reduction in excitability termed 'response depression'. The in vitro slice technique and recordings with sharp electrodes in the current- and voltage-clamp modes were used. Depression was induced by repeatedly stimulating the Schaffer collateral and stratum oriens. Repeated synaptic stimuli also depressed subsequent responses evoked by transmembrane current pulse injection and vice versa. Depression was characterised by a marked decrease in synaptic efficacy that outlasted stimuli for several minutes and was generalized to all pyramidal cells. The action potential frequency adaptation, the slow after-hyperpolarization and the underlying slow Ca2+-dependent K+ current (I(AHP)) were potentiated during depression. The potentiated I(AHP) caused depression by acting as a cumulative negative feedback that reduced synaptic efficacy by increasing the membrane conductance and hyperpolarizing the neurone. This depression may act as a homeostatic negative feedback mechanism to limit the rise in intracellular Ca2+ concentration and stabilize the membrane potential following intense synaptic activation.