For several decades, synaptic plasticity has been considered the best candidate mechanism for the formation and storage of memories. However, efficacy in driving a neuron to fire an action potential (AP) is dependent not only on the size, but also the location and timing of synaptic input, which is subsequently shaped by types and distributions of voltage- and calcium-gated conductances in dendrites. A number of studies, including the original description of long-term potentiation (LTP) 
, have reported that the induction of synaptic plasticity is accompanied by changes in the intrinsic excitability of the neuron, indicating a potential concurrent change in voltage-gated channel activity 
. Ac tivity-dependent regulation of intrinsic excitability has been observed in several invertebrate and vertebrate preparations 
and is induced by learning 
. Changes in voltage-gated channel expression and/or function could mediate these changes in excitably after LTP (intrinsic plasticity). If intrinsic plasticity does act as a memory-storage mechanism 
, it is essential to understand how voltage- and/or calcium-gated channels are modulated and how this plasticity in their function contributes to learning and memory.
With a subthreshold activation range, A-type K+
channels are rapidly activated upon depolarization and so can influence AP onset time, threshold, and inter-spike intervals 
. More recently, a number of other functions for A-type K+
channels have been described, including aiding in AP repolarization, frequency dependent AP broadening, controlling action potential back propagation into dendrites 
, regulating the induction of synaptic plasticity 
and in determining timing of synaptic inputs 
. We have shown that one particular voltage-gated potassium subunit (Kv4.2), controls the initiation, duration and backpropagation of action potentials in CA1 pyramidal neurons from hippocampal organotypic slice cultures 
. Moreover, surface membrane expression of Kv4.2 channels is regulated in an activity- and NMDAR-dependent manner 
. Trafficking of voltage-gated channels therefore provides another way neurons may dynamically regulate excitability in addition to modulation of channel kinetic properties.
The search for the mechanism of intrinsic plasticity has provided evidence for changes in the voltage-dependent properties of a number of ion channels after LTP induction 
. In CA1 dendrites, Frick et al. have shown that LTP induction results in a leftward shift in the voltage-dependence of steady-state inactivation curve of A-type K+
currents in acute hippocampal slices from adult rats 
. This shift has the effect of increasing local dendritic excitability, enhancing action potential back propagation. However, LTP also causes a decrease of AP firing threshold, a global phenomenon 
We show here that LTP induction results in a rapid, long-lasting increase in the intrinsic excitability of CA1 pyramidal neurons from organotypic slice cultures, including a change in initial AP threshold. This LTP-induced increase in excitability was accompanied by a two-phased decrease in A-current activity. Upon LTP induction, we observed in nucleated patches an immediate but transient (~10–20 min) hyperpolarized shift in the voltage-dependence of steady-state inactivation for A-type K+ currents. This shift was accompanied by a progressive, long-term decrease in peak A-type K+ current amplitude that outlasts the observed A-channel inactivation curve shift. Blocking clathrin-mediated endocytosis by intracellular delivery of a dynamin-based inhibitory peptide completely prevented the late expression of LTP and most measures of intrinsic plasticity. Finally we show that this type of plasticity acts globally, with its induction enhancing the synaptic efficacy of un-potentiated synapses. These results indicate that voltage-dependent A-type channels crucially contribute to the enhancement of EPSP-spike coupling with implications for the memory-storage capacity of the hippocampus.