CAMKII Activation Is Not Required for Maintenance of Learning-Induced Enhancement of Neuronal Excitability

Ori Liraz,Edi Barkai,Kobi Rosenblum,Paul A Bartell

doi:10.1371/journal.pone.0004289

Abstract

Pyramidal neurons in the piriform cortex from olfactory-discrimination trained rats show enhanced intrinsic neuronal excitability that lasts for several days after learning. Such enhanced intrinsic excitability is mediated by long-term reduction in the post-burst after-hyperpolarization (AHP) which is generated by repetitive spike firing. AHP reduction is due to decreased conductance of a calcium-dependent potassium current, the sIAHP. We have previously shown that learning-induced AHP reduction is maintained by persistent protein kinase C (PKC) and extracellular regulated kinase (ERK) activation. However, the molecular machinery underlying this long-lasting modulation of intrinsic excitability is yet to be fully described. Here we examine whether the CaMKII, which is known to be crucial in learning, memory and synaptic plasticity processes, is instrumental for the maintenance of learning-induced AHP reduction. KN93, that selectively blocks CaMKII autophosphorylation at Thr286, reduced the AHP in neurons from trained and control rat to the same extent. Consequently, the differences in AHP amplitude and neuronal adaptation between neurons from trained rats and controls remained. Accordingly, the level of activated CaMKII was similar in pirifrom cortex samples taken form trained and control rats. Our data show that although CaMKII modulates the amplitude of AHP of pyramidal neurons in the piriform cortex, its activation is not required for maintaining learning-induced enhancement of neuronal excitability.

Highlights

Learning-induced cellular changes can be divided into two general groups: modifications that occur at synapses and modifications in the intrinsic properties of the neurons
In most piriform cortex pyramidal neurons, the peak of the post burst AHP is mediated by two calcium activated potassium currents, the IAHP and the sIAHP [13]
To date the role of calmodulin-dependent kinase II (CaMKII) in memory formation and maintenance was mostly thought to occur via its effects on synaptic transmission, it may act on intrinsic neuronal properties

Summary

Introduction

Learning-induced cellular changes can be divided into two general groups: modifications that occur at synapses and modifications in the intrinsic properties of the neurons. Learning induced enhancement in neuronal excitability was shown in hippocampal neurons following classical conditioning [4,5], water-maze training (Oh et al, 2003), and in piriform cortex neurons following olfactory-discrimination (OD) learning This enhanced excitability is manifested by reduced spike frequency adaptation [4,6], and lasts for several days after training completion [1]. It was recently shown that only the apamin-insensitive portion of the post-burst AHP is reduced after olfactory-discrimination learning [13], suggesting that learning modulates the sIAHP. Changes in the sIAHP were implicated in learning-related modifications in hippocampal neurons after spatial learning [14]

Objectives

Methods

Results

Conclusion