The activity-dependent potentiation of the slow Ca2+-activated K+ current regulates synaptic efficacy in rat CA1 pyramidal neurons

Activity-dependent modifications of neuronal excitability are of key functi onal 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 acti vity-dependent reduction in excitability termed "response depression". The in vitro slice technique and recordings with sharp electrodes in the curren t- and voltage-clamp modes were used. Depression was induced by repeatedly stimulating the Schaffer collateral and stratum oriens. Repeated synaptic s timuli also depressed subsequent responses evoked by transmembrane current pulse injection and vice versa. Depression was characterised by a marked de crease in synaptic efficacy that outlasted stimuli for several minutes and was generalized to all pyramidal cells. The action potential frequency adap tation, the slow after-hyperpolarization and the underlying slow Ca2+-depen dent K+ current (I-AHP) were potentiated during depression. The potentiated I-AHP caused depression by acting as a cumulative negative feedback that r educed synaptic efficacy by increasing the membrane conductance and hyperpo larizing the neurone. This depression may act as a homeostatic negative fee dback mechanism to limit the rise in intracellular Ca2+ concentration and s tabilize the membrane potential following intense synaptic activation.