Computer models predict differential dendritic vulnerability with ischemia and spreading depression

The useful part

McDougal Ischemia, whether abrupt or chronic, limits ATP production and disrupts ATP-dependent homeostatic mechanisms, leading to alterations in both intracellular and extracellular ion concentrations. When the depolarizing effects are strong enough, the cells undergo depolarization blockade, known as spreading depression. We hypothesized that consequences of ischemic or SD homeostatic failure would differ on the subcellular scale, with differences between disjunct dendritic regions of a hippocampal CA1 pyramidal neuron.

How it works

• In both cases, calcium accumulation was greatest in the basal dendrites, suggesting these dendrites would show the greatest effects of excitotoxicity.
• To evaluate the interplay between morphology and ion concentrations, we used a mechanistic simulation incorporating neuronal morphology, pumps, exchangers, voltage-, and Ca 2+ -sensitive ion channels.
• By contrast, in ischemia, but not in SD, distal apical dendrites were exposed to greater intracellular chloride concentrations, which may lead to dendritic beading.