Depolarization promotes neuronal survival through moderate increases in Ca2+ influx, but the effects of survival-promoting depolarization (vs conventional trophic support) on neuronal signaling are poorly characterized. We found that chronic, survival-promoting depolarization, but not conventional trophic support, selectively decreased the somatic Ca2+ current density in hippocampal and cerebellar granule neurons. Depolarization rearing depressed multiple classes of high-voltage activated Ca2+ current. Consistent with the idea that these changes also affected synaptic Ca2+ channels, chronic depolarization presynaptically depressed hippocampal neurotransmission. Six days of depolarization rearing completely abolished glutamate transmission but altered GABA transmission in a manner consistent with the alterations of Ca2+ current. The continued survival of depolarization-reared neurons was extremely sensitive to the re-establishment of basal culture conditions and was correlated with the effects on intracellular Ca2+ concentration. Thus, compared with cells reared on conventional trophic factors, depolarization evokes homeostatic changes in Ca2+ influx and signaling that render neurons vulnerable to cell death on activity reduction.

Original languageEnglish
Pages (from-to)1825-1831
Number of pages7
JournalJournal of Neuroscience
Issue number5
StatePublished - Mar 1 2003


  • Depolarization
  • GABA
  • Glutamate
  • HVA Ca current
  • Neuronal survival
  • Synaptic depression


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