Autophosphorylation of alphaCaMKII downregulates excitability of CA1 pyramidal neurons following synaptic stimulation.
It has been well documented that alpha-calcium/calmodulin-dependent protein kinase II (alphaCaMKII) 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 alphaCaMKII may regulate neuronal excitability remain unclear. Here, we report that alphaCaMKII knock-in mice with a targeted T286A point mutation that prevents its autophosphorylation (alphaCaMKII(T286A)) 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 alphaCaMKII(T286A) 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 alphaCaMKII 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.
Sametsky
Evgeny A
EA
Department of Physiology, Northwestern University Feinberg School of Medicine, Chicago, IL 60611-3008, USA.
Disterhoft
John F
JF
Ohno
Masuo
M
D000704:Analysis of Variance; D000818:Animals; D054732:Calcium-Calmodulin-Dependent Protein Kinase Type 2 / Q000235:genetics / Q000378:metabolism*; D004558:Electric Stimulation; D055879:Gene Knock-In Techniques; D006624:Hippocampus / Q000502:physiology; D066298:In Vitro Techniques; D008564:Membrane Potentials / Q000502:physiology; D051379:Mice; D009473:Neuronal Plasticity / Q000502:physiology; D018408:Patch-Clamp Techniques; D010766:Phosphorylation; D017354:Point Mutation; D017966:Pyramidal Cells / Q000502:physiology*; D009435:Synaptic Transmission / Q000502:physiology*
D054732:Calcium-Calmodulin-Dependent Protein Kinase Type 2