Autophosphorylation of alpha CaMKII downregulates excitability of CA1 pyramidal neurons following synaptic stimulation

作者：Sametsky Evgeny A; Disterhoft John F; Ohno Masuo^*

来源：Neurobiology of Learning and Memory, 2009, 92(1): 120-123.

DOI：10.1016/j.nlm.2009.02.006

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

It has been well documented that alpha-calcium/calmodulin-dependent protein kinase II (alpha CaMKII) 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 alpha CaMKII may regulate neuronal excitability remain unclear. Here, we report that alpha CaMKII knock-in mice with a targeted T286A point mutation that prevents its autophosphorylation (alpha CaMKII(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 alpha CaM-KII(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 alpha CaMKII 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.

• 出版日期2009-7
• 单位西北大学