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In the present study we used an organotypic slice culture of chick embryo spinal cord to explore the responsiveness of mature MNs to different excitotoxic stimuli and mitrochondrial inhibition. We found that, in this system, MNs are highly vulnerable to excitotoxins such as glutamate, N\u2010methyl\u2010D\u2010aspartate (NMDA), and kainate (KA), and that the neuroprotective drug riluzole rescues MNs from KA\u2010mediated excitotoxic death. MNs are also sensitive to chronic mitochondrial inhibition induced by malonate and 3\u2010nitropropionic acid (3\u2010NP) in a dose\u2010dependent manner. MN degeneration induced by treatment with mitochondrial toxins displays structural changes similar to those seen following excitotoxicity and can be prevented by applying either the antiexcitotoxic drug 6\u2010cyano\u20107\u2010nitroquinoxaline\u20102,3\u2010dione disodium (CNQX) or riluzole. Excitotoxicity results in an increased frequency of normal spontaneous Ca<jats:sup>2+<\/jats:sup>oscillations in MNs, which is followed by a sustained deregulation of intracellular Ca<jats:sup>2+<\/jats:sup>. Tolerance to excitotoxic MN death resulting from chronic exposure to excitotoxins correlates with a reduced excitotoxin\u2010induced increase in intracellular Ca<jats:sup>2+<\/jats:sup>and increased thapsigargin\u2010sensitive Ca<jats:sup>2+<\/jats:sup>stores. J. Comp. Neurol. 516:277\u2013290, 2009. \u00a9 2009 Wiley\u2010Liss, Inc.<\/jats:p>","DOI":"10.1002\/cne.22118","type":"journal-article","created":{"date-parts":[[2009,6,11]],"date-time":"2009-06-11T13:01:01Z","timestamp":1244725261000},"page":"277-290","source":"Crossref","is-referenced-by-count":17,"title":["Excitotoxic motoneuron degeneration induced by glutamate receptor agonists and mitochondrial toxins in organotypic cultures of chick embryo spinal cord"],"prefix":"10.1002","volume":"516","author":[{"given":"N\u00faria","family":"Brunet","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Olga","family":"Tarabal","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Josep 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