Short Trains of Theta Frequency Stimulation Enhance CA1 Pyramidal Neuron Excitability in the Absence of Synaptic Potentiation

Abstract

Although plasticity at excitatory synapses is widely studied as a mechanism for memory formation, less is known about the properties and mechanisms underlying activity-dependent changes in excitability. Using extracellular and intracellular recordings in hippocampal slices, we find that short trains (2-3 s) of Schaffer collateral fiber stimulation delivered at 5 Hz induce a robust and persistent increase in the excitability of CA1 pyramidal cells in the absence of synaptic potentiation. This change in excitability is input specific, NMDA receptor dependent, and is not accompanied by lasting changes in either inhibitory synaptic transmission or somatic excitability. Although many of these properties are similar to those seen in synaptic long-term potentiation (LTP), the increase in CA1 pyramidal cell excitability was not blocked by inhibitors of several protein kinases required for the induction of LTP by theta frequency stimulation. Instead, 5 Hz stimulation-induced changes in neuronal excitability were blocked by inhibitors of the protein phosphatase calcineurin. Together, our results suggest that very brief bouts of theta frequency synaptic activity induce a selective, persistent, and dendritically localized increase in CA1 pyramidal cell excitability that might have an important role in both information storage and metaplasticity.