Elevation of extracellular potassium facilitates the induction of hippocampal long‐term potentiation

Hippocampal long‐term potentiation (LTP) is widely believed to be a cellular substrate for learning and memory. A likely physiological stimulus for initiating LTP is repetitive neuronal activity, which also results in K+ accumulation extracellularly. Therefore, the involvement of elevated extracellular K+ concentrations in the induction of LTP of the stratum radiatum‐CA1 neuronal synapse was investigated in the hippocampal slice preparation. Increasing the K+ content in extracellular perfusing medium from 3.1 to 15 mM resulted in facilitation of LTP induction in weak excitatory postsynaptic potentials (EPSPs). Since changes that occur to generate LTP are thought to be localized to synaptic regions, it would be relevant to selectively increase synaptic K+ levels. To this end, the following experiments were conducted: (i) baclofen, a GABAB receptor agonist which, in addition to having a disinhibitory presynaptic action, activates a K+ conductance in CA1 neuronal dendrites, was applied to the slice; (ii) K+ was directly applied by iontophoresis. At a concentration of 5 μM baclofen, as well as with K+ iontophoresis (200–300 nA), LTP of weak EPSPs was facilitated. The present data suggest that an increase in synaptic K+ levels can fulfill the condition of cooperativity for LTP induction, raising the possibility that an elevation of this monovalent ion plays a physiological role in triggering LTP. © 1992 Wiley‐Liss, Inc.