Autophosphorylation of αCaMKII downregulates excitability of CA1 pyramidal neurons following synaptic stimulation

Evgeny A. Sametsky, John F. Disterhoft, Masuo Ohno*

*Corresponding author for this work

Research output: Contribution to journalArticle

10 Scopus citations

Abstract

It has been well documented that α-calcium/calmodulin-dependent protein kinase II (αCaMKII) is central to synaptic plasticity such as long-term potentiation, an activity-dependent strengthening of synapses that is thought to underlie certain types of learning and memory. However, the mechanisms by which αCaMKII may regulate neuronal excitability remain unclear. Here, we report that αCaMKII knock-in mice with a targeted T286A point mutation that prevents its autophosphorylation (αCaMKIIT286A) showed increased excitability of CA1 pyramidal neurons compared with wild-type controls, as measured by a decrease in the slow component of post-burst afterhyperpolarization (sAHP) following high-frequency stimulation of Schaffer collateral afferent fibers. In contrast, AHP was indistinguishable between αCaMKIIT286A and wild-type mice when it was evoked by somatic current injections, indicating that the hyperexcitability is observed specifically in response to synaptic stimulation in this mutant. Taken together, our results suggest that αCaMKII functions to downregulate CA1 neuron excitability following synaptic stimulation, presumably supporting the functionally adaptive modulation of excitability during hippocampal learning or providing a negative feedback mechanism that would prevent neurons from becoming hyperexcitable and promote network stability.

Original languageEnglish (US)
Pages (from-to)120-123
Number of pages4
JournalNeurobiology of Learning and Memory
Volume92
Issue number1
DOIs
StatePublished - Jul 1 2009

Keywords

  • Afterhyperpolarization (AHP)
  • CA1
  • Excitability
  • Hippocampus
  • Schaffer collateral
  • T286A
  • α-Calcium/calmodulin-dependent protein kinase II

ASJC Scopus subject areas

  • Experimental and Cognitive Psychology
  • Cognitive Neuroscience
  • Behavioral Neuroscience

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