Regulation of hippocampal sharp waves by Ca2+-dependent slow after hyperpolarization.

Abstract

In rodent hippocampal pyramidal neurons, repetitive discharges are followed by a slow afterhyperpolarization (sAHP) as a result of activation of a Ca2+-dependent K+ current. The sAHP is sensitive to activation of several G-protein coupled neurotransmitter receptors and downstream signal cascades. Modulations of the sAHP have been shown to be closely associated with synaptic plasticity, learning, and aging processes. However, it is presently unclear whether the sAHP generation is involved in hippocampal network activities. We explored this issue using an in vitro (thick-slice) model of mouse hippocampal sharp waves. Our data show that the sAHP occurs in CA3 pyramidal neurons following each sharp wave event and sAHP suppression is associated with a large increase in occurrence frequency of spontaneous sharp waves. Considering that sharp waves are important for hippocampal-cortical communication and memory processes, we postulate that the sAHP serves as an intrinsic regulatory mechanism of sharp waves and plays a significant role in hippocampus-dependent cognitive functions.