Role of Ca2+/calmodulin-dependent protein kinase II in dendritic spine remodeling during epileptiform activity in vitro

Xiang-ming Zha; Michael E Dailey; Steven H Green

doi:10.1002/jnr.22033

Back

Role of Ca2+/calmodulin-dependent protein kinase II in dendritic spine remodeling during epileptiform activity in vitro

Journal article

Peer reviewed

Role of Ca2+/calmodulin-dependent protein kinase II in dendritic spine remodeling during epileptiform activity in vitro

Xiang-ming Zha, Michael E Dailey and Steven H Green

Journal of neuroscience research, Vol.87(9), pp.1969-1979

07/2009

DOI: 10.1002/jnr.22033

PMCID: PMC2694514

PMID: 19235894

Files and links (1)

url

http://doi.org/10.1002/jnr.22033View

Open Access

Abstract

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.

Disks Large Homolog 4 Protein

Pseudopodia - ultrastructure

Synaptic Transmission - physiology

Protein Transport - physiology

Green Fluorescent Proteins - genetics

Intracellular Signaling Peptides and Proteins - metabolism

Epilepsy - physiopathology

Recombinant Fusion Proteins - metabolism

Cerebral Cortex - ultrastructure

Neuronal Plasticity - physiology

Pseudopodia - enzymology

Membrane Proteins - metabolism

Intracellular Signaling Peptides and Proteins - genetics

Pyramidal Cells - ultrastructure

Organ Culture Techniques

Calcium-Calmodulin-Dependent Protein Kinase Type 2 - metabolism

Animals, Newborn

Epilepsy - enzymology

Green Fluorescent Proteins - metabolism

Cerebral Cortex - enzymology

Membrane Proteins - genetics

Dendritic Spines - enzymology

Rats

Pyramidal Cells - enzymology

Synaptic Membranes - ultrastructure

Synaptic Membranes - enzymology

Animals

Recombinant Fusion Proteins - genetics

Luminescent Proteins - genetics

Dendritic Spines - ultrastructure

Luminescent Proteins - metabolism

Details

Title: Subtitle: Role of Ca2+/calmodulin-dependent protein kinase II in dendritic spine remodeling during epileptiform activity in vitro
Creators: Xiang-ming Zha - Department of Biology, University of Iowa, Iowa City, IA 52242-1324, USA
Michael E Dailey
Steven H Green
Resource Type: Journal article
Publication Details: Journal of neuroscience research, Vol.87(9), pp.1969-1979
DOI: 10.1002/jnr.22033
PMID: 19235894
PMCID: PMC2694514
NLM abbreviation: J Neurosci Res
ISSN: 0360-4012
eISSN: 1097-4547
Publisher: United States
Grant note: R01 DC002961-12 / NIDCD NIH HHS\nR29 NS037159 / NINDS NIH HHS\nS10 RR017941 / NCRR NIH HHS\nDC002961 / NIDCD NIH HHS\nR01 DC002961 / NIDCD NIH HHS
Language: English
Date published: 07/2009
Academic Unit: Iowa Neuroscience Institute; Biology; Otolaryngology
Record Identifier: 9984070361402771

Metrics

9 Record Views

17 Times Cited - Web of Science