Spinal motor neurons are more vulnerable than GABAergic cortical neurons to AMPA/kainate receptor-mediated injury.A, Slowly triggered neurotoxicity. Spinal or cortical cultures were exposed to kainate (5–10 μm + 10 μm MK-801) or AMPA (2.5–5 μm + 10 μm MK-801) for 24 hr, followed by assessment of injury. Identification of motor neurons was based on morphology and staining for SMI-32; GABAergic cortical neurons were identified by staining for GAD. Injury to the overall spinal population (gray bars) and cortical population (hatched bars) was assessed by LDH measurement, whereas injury to motor neurons (black bars) and GABAergic cortical neurons (white bars) was assessed by direct cell counts (see Materials and Methods). B, Rapidly triggered neurotoxicity. Spinal or cortical cultures were exposed to AMPA (50 μm + 10 μm MK-801; 10 min), either alone (left) or in the presence of the AMPA receptor desensitization inhibitor cyclothiazide (100 μm;right), in either Ca2+-containing or Ca2+-free buffer as indicated. Twenty-four hours after the exposure, injury was assessed as described above. Values represent the means ± SEM compiled from at least four experiments; n = 10–12 cultures per condition. Anasterisk indicates motor neuron or GABAergic cell loss significantly different from overall cell loss; anampersand indicates motor neuron cell loss significantly different from GABAergic cell loss (p < 0.01 by two-tailed t test).