Abstract
Since its original description, the induction of synaptic long-term potentiation (LTP) has been known to be accompanied by a lasting increase in the intrinsic excitability (intrinsic plasticity) of hippocampal neurons. Recent evidence shows that dendritic excitability can be enhanced by an activity-dependent decrease in the activity of A-type K+ channels. In the present manuscript, we examined the role of A-type K+ channels in regulating intrinsic excitability of CA1 pyramidal neurons of the hippocampus after synapse-specific LTP induction. In electrophysiological recordings we found that LTP induced a potentiation of excitability which was accompanied by a two-phased change in A-type K+ channel activity recorded in nucleated patches from organotypic slices of rat hippocampus. Induction of LTP resulted in an immediate but short lasting hyperpolarization of the voltage-dependence of steady-state A-type K+ channel inactivation along with a progressive, long-lasting decrease in peak A-current density. Blocking clathrin-mediated endocytosis prevented the A-current decrease and most measures of intrinsic plasticity. These results suggest that two temporally distinct but overlapping mechanisms of A-channel downregulation together contribute to the plasticity of intrinsic excitability. Finally we show that intrinsic plasticity resulted in a global enhancement of EPSP-spike coupling.
Highlights
For several decades, synaptic plasticity has been considered the best candidate mechanism for the formation and storage of memories
Having recently described the activity-dependent trafficking of the A-type K+ channel subunit Kv4.2 in hippocampal neurons [12], we hypothesized that A-channel internalization contributes to intrinsic excitability changes observed in CA1 hippocampal pyramidal neurons after synaptic long-term potentiation (LTP) induction [1,19]
Global effect of intrinsic plasticity on dendritic integration These results presented so far, along with previous results showing an effect of A-type K+ channels on synaptic currents [9,12,22,23], suggests the targeting A-type channels for activity-dependent regulation of intrinsic and synaptic plasticity
Summary
Synaptic plasticity has been considered the best candidate mechanism for the formation and storage of memories. Efficacy in driving a neuron to fire an action potential (AP) is dependent on the size, and 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) [1], 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 [2,3]. 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 [4], 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
Sign-in/Register to view highlights & summary 
Published Version (
Free)
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a call