期刊
JOURNAL OF NEUROSCIENCE RESEARCH
卷 87, 期 9, 页码 1969-1979出版社
WILEY
DOI: 10.1002/jnr.22033
关键词
epileptiform activity; CaMKII; hippocampal slice culture; postsynaptic density; synaptogenesis
资金
- American Heart Association [0655764Z]
- NIH [DC002961]
- UI Biosciences Initiative pilot Grant
- NATIONAL CENTER FOR RESEARCH RESOURCES [S10RR017941] Funding Source: NIH RePORTER
- NATIONAL INSTITUTE OF NEUROLOGICAL DISORDERS AND STROKE [R29NS037159] Funding Source: NIH RePORTER
- NATIONAL INSTITUTE ON DEAFNESS AND OTHER COMMUNICATION DISORDERS [R01DC002961] Funding Source: NIH RePORTER
Epileptiform activity (EA) in vivo and in vitro induces a loss of dendritic spines and synapses. Because CaMKII has been implicated in synaptogenesis and synaptic plasticity, we investigated the role of CaMKII in the effects of EA on spines, using rat hippocampal slice cultures. To visualize dendrites and postsynaptic densities (PSDs) in pyramidal neurons in the slices, we used biolistic transfection to express either free GFP or a PSD95-YFP construct that specifically labels PSDs. This allowed us to distinguish two classes of dendritic protrusions: spines that contain PSDs, and filopodia that lack PSDs and that are, on average, longer than spines. By these criteria, 48 hr of EA caused a decrease specifically in the number of spines. Immunoblots showed that EA increased CaMKII activity in the slices. Inhibition of CaMKII by expression of AIP, a specific peptide inhibitor of CaMKII, reduced spine number under basal conditions and failed to prevent EA-induced spine loss. However, under EA conditions, AIP increased the number of filopodia and the number of PSDs on the dendritic shaft. These data show at least two roles for CaMKII activity in maintenance and remodeling of dendritic spines under basal or EA conditions. First, CaMKII activity promotes the maintenance of spines and spine PSDs. Second, CaMKII activity suppresses EA-induced formation of filopodia and suppresses an increase in shaft PSDs, apparently by promoting translocation of PSDs from dendritic shafts to spines and/or selectively stabilizing spine rather than shaft PSDs. (C) 2009 Wiley-Liss, Inc.
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