TY - JOUR T1 - Homeostatic Effects of Depolarization on Ca<sup>2+</sup> Influx, Synaptic Signaling, and Survival JF - The Journal of Neuroscience JO - J. Neurosci. SP - 1825 LP - 1831 DO - 10.1523/JNEUROSCI.23-05-01825.2003 VL - 23 IS - 5 AU - Krista L. Moulder AU - Robert J. Cormier AU - Amanda A. Shute AU - Charles F. Zorumski AU - Steven Mennerick Y1 - 2003/03/01 UR - http://www.jneurosci.org/content/23/5/1825.abstract N2 - 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. ER -