Differential effects of αCaMKII mutation on hippocampal learning and changes in intrinsic neuronal excitability

Masuo Ohno*, Evgeny A. Sametsky, Alcino J. Silva, John F. Disterhoft

*Corresponding author for this work

Research output: Contribution to journalArticle

27 Scopus citations


α-Calcium/calmodulin-dependent kinase II (αCaMKII) is central to synaptic plasticity but it remains unclear whether this kinase contributes to neuronal excitability changes, which are a cellular correlate of learning. Using knock-in mice with a targeted T286A mutation that prevents the autophosphorylation of αCaMKII (αCaMKIIT286A), we studied the role of αCaMKII signaling in regulating hippocampal neuronal excitability during hippocampus-dependent spatial learning in the Morris water maze. Wild-type control mice showed increased excitability of CA1 pyramidal neurons, as assessed by a reduction in the postburst afterhyperpolarization (AHP), after spatial training in the water maze. Importantly, wild-type mice did not show AHP changes when they were exposed to the water maze without the escape platform and swam the same amount of time as the trained mice (swim controls), thus manifesting learning-specific increases in hippocampal CA1 excitability associated with spatial training. Meanwhile, αCaMKIIT286A mice showed impairments in spatial learning but exhibited reduced levels of AHP that were similarq1 to wild-type controls after water-maze training. Notably, both trained and swim-control groups of αCaMKIIT286A mutants showed similar increased excitability, indicating that swimming by itself is enough to induce changes in excitability in the absence of normal αCaMKII function. This result demonstrates dissociation of αCaMKII-independent changes in intrinsic neuron excitability from learning and synaptic plasticityq2 mechanisms, suggesting that increases in excitability per se are not perfectly correlated with learning. Our findings suggest that αCaMKII signaling may function to suppress learning-unrelated changes during training, thereby allowing hippocampal CA1 neurons to increase their excitability appropriately for encoding spatial memories.

Original languageEnglish (US)
Pages (from-to)2235-2240
Number of pages6
JournalEuropean Journal of Neuroscience
Issue number8
StatePublished - Apr 2006


  • Afterhyperpolarization
  • CA1 pyramidal neurons
  • Calcium
  • Calmodulin-dependent kinase II
  • Hippocampus
  • Water maze

ASJC Scopus subject areas

  • Neuroscience(all)

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