%0 Journal Article %A C. William R. Shuttleworth %A John A. Connor %T Strain-Dependent Differences in Calcium Signaling Predict Excitotoxicity in Murine Hippocampal Neurons %D 2001 %R 10.1523/JNEUROSCI.21-12-04225.2001 %J The Journal of Neuroscience %P 4225-4236 %V 21 %N 12 %X Commonly used inbred murine strains differ substantially in their vulnerability to excitotoxic insults. We investigated whether differences in dendritic Ca2+ signaling could underlie the differential vulnerability of C57BL/6 (resistant to kainate excitotoxicity) and C57BL/10 strains (vulnerable). A striking difference was found in fine dendrite Ca2+ responses after kainate exposure. Ca2+ signals in distal dendrites were large in C57BL/10 neurons, and, if a threshold concentration of ∼1.5 μm was reached, a region of sustained high Ca2+ was established in the distal dendritic tree. This region then served as an initiation site for a degenerative cascade, producing high Ca2+ levels that slowly spread to involve the entire neuron and led to cell death. Dendritic Ca2+ signals in C57BL/6 neurons were much smaller and did not trigger these propagating secondary responses. Strain differences in dendritic Ca2+ signaling were also evident after tetanic stimulation of Schaffer collaterals. Ca2+ responses were much larger and peaked earlier in distal dendrites of C57BL/10 compared with those in C57BL/6. Neurons from both strains had similar membrane properties and responded to kainate with intense action potential firing. Degenerative Ca2+ responses were seen in both strains if soma Ca2+ could be sustained above 1.5 μm. The early phases of secondary Ca2+ responses were attributable to Ca2+ influx and were abolished rapidly by buffered zero Ca2+ saline. Taken together, these data indicate that the substantial difference in Ca2+ signals in fine distal dendrites and in the initiation of spreading secondary responses may underlie the selective vulnerability of these neurons to excitotoxic insults. %U https://www.jneurosci.org/content/jneuro/21/12/4225.full.pdf