Document Detail


Homeostatic plasticity in hippocampal slice cultures involves changes in voltage-gated Na+ channel expression.
MedLine Citation:
PMID:  14751586     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
Neurons preserve stable electrophysiological properties despite ongoing changes in morphology and connectivity throughout their lifetime. This dynamic compensatory adjustment, termed 'homeostatic plasticity', may be a fundamental means by which the brain normalizes its excitability, and is possibly altered in disease states such as epilepsy. Despite this significance, the cellular mechanisms of homeostatic plasticity are incompletely understood. Using field potential analyses, we observed a compensatory enhancement of neural excitability after 48 h of activity deprivation via tetrodotoxin (TTX) in hippocampal slice cultures. Because activity deprivation can enhance voltage-gated sodium channel (VGSC) currents, we used Western blot analyses to probe for these channels in control and activity-deprived slice cultures. A significant upregulation of VGSCs expression was evident after activity deprivation. Furthermore, immunohistochemistry revealed this upregulation to occur along primarily pyramidal cell dendrites. Western blot analyses of cultures after 1 day of recovery from activity deprivation showed that VGSC levels returned to control levels, indicating that multiple molecular mechanisms contribute to enhanced excitability. Because of their longevity and in vivo-like cytoarchitecture, we conclude that slice cultures may be highly useful for investigating homeostatic plasticity. Furthermore, we demonstrate that enhanced excitability involves changes in channel expression with a targeted localization likely profound transform the integrative capacities of hippocampal pyramidal cells and their dendrites.
Authors:
Caitlin O Aptowicz; Phillip E Kunkler; Richard P Kraig
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't; Research Support, U.S. Gov't, P.H.S.    
Journal Detail:
Title:  Brain research     Volume:  998     ISSN:  0006-8993     ISO Abbreviation:  Brain Res.     Publication Date:  2004 Feb 
Date Detail:
Created Date:  2004-01-30     Completed Date:  2004-04-15     Revised Date:  2014-09-20    
Medline Journal Info:
Nlm Unique ID:  0045503     Medline TA:  Brain Res     Country:  Netherlands    
Other Details:
Languages:  eng     Pagination:  155-63     Citation Subset:  IM    
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MeSH Terms
Descriptor/Qualifier:
Anesthetics, Local / pharmacology
Animals
Blotting, Western
Electrophysiology
Hippocampus / drug effects,  physiology*
Homeostasis / physiology
Immunohistochemistry
Nerve Net / physiology*
Neuronal Plasticity / drug effects,  physiology*
Organ Culture Techniques
Potassium Channels, Voltage-Gated / biosynthesis*,  drug effects
Rats
Rats, Wistar
Tetrodotoxin / pharmacology
Up-Regulation
Grant Support
ID/Acronym/Agency:
NS-19108/NS/NINDS NIH HHS; R01 NS019108/NS/NINDS NIH HHS; R01 NS019108-24/NS/NINDS NIH HHS
Chemical
Reg. No./Substance:
0/Anesthetics, Local; 0/Potassium Channels, Voltage-Gated; 4368-28-9/Tetrodotoxin
Comments/Corrections

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