Activity-induced Polo-like kinase 2 is required for homeostatic plasticity of hippocampal neurons during epileptiform activity.
Homeostatic plasticity mechanisms stabilize the activity of a neuron or neuronal circuit during prolonged periods of increased network activity and have been proposed to function in the prevention of epilepsy. How homeostatic plasticity is achieved at the molecular level during hyperactivity states in general, and during epileptiform activity in particular, is unclear. Using organotypic hippocampal slice cultures as a model system, we found that the protein kinase Polo-like kinase 2 (Plk2) was induced during prolonged epileptiform activity and was required for the activity-dependent reduction in membrane excitability of pyramidal neurons. Disruption of Plk2 function by dominant-negative or RNA interference not only blocked the downregulation of membrane excitability during epileptiform activity, but also unmasked a slow and progressive potentiation in synaptic strength that prevented the ability of the slice to undergo long-term potentiation. Thus, Plk2 function is required to prevent escalating potentiation and maintain synapses in a plastic state during epileptiform activity in hippocampal slice cultures.
Seeburg
Daniel P
DP
The Picower Institute for Learning and Memory, RIKEN-Massachusetts Institute of Technology Neuroscience Research Center, Howard Hughes Medical Institute, Massachusetts Institute of Technology, Cambridge, Massachusetts 02139, USA.
Sheng
Morgan
M
D000200:Action Potentials / Q000235:genetics; D000818:Animals; D002462:Cell Membrane / Q000235:genetics / Q000378:metabolism; D015536:Down-Regulation / Q000235:genetics; D004827:Epilepsy / Q000201:enzymology* / Q000503:physiopathology; D006624:Hippocampus / Q000201:enzymology* / Q000503:physiopathology; D006706:Homeostasis / Q000235:genetics; D017774:Long-Term Potentiation / Q000235:genetics; D009473:Neuronal Plasticity / Q000502:physiology*; D009474:Neurons / Q000201:enzymology*; D009924:Organ Culture Techniques; D018408:Patch-Clamp Techniques; D011494:Protein Kinases / Q000235:genetics / Q000378:metabolism*; D017346:Protein Serine-Threonine Kinases / Q000235:genetics / Q000378:metabolism*; D017966:Pyramidal Cells / Q000378:metabolism; D034622:RNA Interference / Q000502:physiology; D051381:Rats; D014162:Transfection
D011494:Protein Kinases; D017346:Protein Serine-Threonine Kinases; C530504:Plk2 protein, rat; C444640:serum-inducible kinase