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Because NMDA receptors play a crucial role in neurodegeneration, we have compared the response to exogenous NMDA in CA1 pyramidal cells and interneurons of the stratum oriens using combined whole\u2010cell patch\u2010clamp recording and ratiometric Ca<jats:sup>2+<\/jats:sup> imaging. In voltage\u2010clamp, current\u2010clamp or in nominally Mg<jats:sup>2+<\/jats:sup>\u2010free medium, NMDA (10\u2003\u00b5<jats:sc>m<\/jats:sc>; 3\u20135\u2003min exposure in the presence of tetrodotoxin) induced a markedly larger inward current and Ca<jats:sup>2+<\/jats:sup> rise in pyramidal cells than in interneurons. Pyramidal cells also showed a more pronounced voltage dependence in their response to NMDA. We hypothesized that this enhanced response to NMDA receptor activation in pyramidal cells could underlie their increased vulnerability to excitotoxicity. Using loss of dye as an indicator of degenerative membrane disruption, interneurons tolerated continuous exposure to a high concentration of NMDA (30\u2003\u00b5<jats:sc>m<\/jats:sc>) for longer periods than pyramidal cells. This acute neurodegeneration in pyramidal cells was independent of intracellular Ca<jats:sup>2+<\/jats:sup>, because high intracellular BAPTA (20\u2003m<jats:sc>m<\/jats:sc>) did not prolong survival time. Thus, a plausible explanation for the enhanced sensitivity of pyramidal neurons to excitotoxic insults associated with cerebral ischemia is their greater response to NMDA receptor activation, which may reflect differences in NMDA receptor expression and\/or subunit composition.<\/jats:p>","DOI":"10.1111\/j.1460-9568.2005.04497.x","type":"journal-article","created":{"date-parts":[[2005,12,8]],"date-time":"2005-12-08T12:59:44Z","timestamp":1134046784000},"page":"3077-3090","update-policy":"http:\/\/dx.doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":25,"title":["Differential responses to NMDA receptor activation in rat hippocampal interneurons and pyramidal cells may underlie enhanced pyramidal cell vulnerability"],"prefix":"10.1111","volume":"22","author":[{"given":"E.","family":"Avignone","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"B. 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