title: Homeostatic plasticity in hippocampal slice cultures involves changes in voltage-gated Na+ channel expression.
abstract: 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.affiliation: Committee on Neurobiology, The University of Chicago, Chicago, IL 60637, USA
authors.forename: Caitlin O
authors.initials: CO
authors.lastname: Aptowicz
authors.forename: Phillip E
authors.initials: PE
authors.lastname: Kunkler
authors.forename: Richard P
authors.initials: RP
authors.lastname: Kraig
mesh_terms: D000779:Anesthetics, Local / Q000494:pharmacology; D000818:Animals; D015153:Blotting, Western; D004594:Electrophysiology; D006624:Hippocampus / Q000187:drug effects / Q000502:physiology*; D006706:Homeostasis / Q000502:physiology; D007150:Immunohistochemistry; D009415:Nerve Net / Q000502:physiology*; D009473:Neuronal Plasticity / Q000187:drug effects / Q000502:physiology*; D009924:Organ Culture Techniques; D024642:Potassium Channels, Voltage-Gated / Q000096:biosynthesis* / Q000187:drug effects; D051381:Rats; D017208:Rats, Wistar; D013779:Tetrodotoxin / Q000494:pharmacology; D015854:Up-Regulation
chemical_list: D000779:Anesthetics, Local; D024642:Potassium Channels, Voltage-Gated; D013779:Tetrodotoxin