A novel short‐term plasticity of intrinsic excitability in the hippocampal CA1 pyramidal cells

Key points Changes in neuronal activity often trigger compensatory mechanisms that stabilize neuron output. We have identified a novel form of short-term plasticity of membrane excitability, which develops early after the eye-opening period in rats. Holding the membrane potential of CA1 neurons at subthreshold depolarization from 15 s to several minutes induces a reduction of the excitability. This plasticity requires an influx of T-type Ca2+ current that modulates the A-type K+ current. These results help us understand that the resting potential history could modify cell intrinsic excitability. Abstract Changes in neuronal activity often trigger compensatory mechanisms aimed at regulating network activity homeostatically. Here we have identified and characterized a novel form of compensatory short-term plasticity of membrane excitability, which develops early after the eye-opening period in rats (P16–19 days) but not before that developmental stage (P9–12 days old). Holding the membrane potential of CA1 neurons right below the firing threshold from 15 s to several minutes induced a potentiation of the repolarizing phase of the action potentials that contributed to a decrease in the firing rate of CA1 pyramidal neurons in vitro. Furthermore, the mechanism for inducing this plasticity required the action of intracellular Ca2+ entering through T-type Ca2+ channels. This increase in Ca2+ subsequently activated the Ca2+ sensor K+ channel interacting protein 3, which led to the increase of an A-type K+ current. These results suggest that Ca2+ modulation of somatic A-current represents a new form of homeostatic regulation that provides CA1 pyramidal neurons with the ability to preserve their firing abilities in response to membrane potential variations on a scale from tens of seconds to several minutes.