Spreading depolarization triggered by elevated potassium is weak or absent in the rodent lower brain

Abstract

We examined in live coronal slices from rat and mouse which brain regions generate potassium-triggered spreading depolarization (SD Kt). This technique simulates cortical spreading depression, which underlies migraine aura in the intact brain. An SD Kt episode was evoked by increasing bath [K+ ] o and recorded as a propagating front of elevated light transmittance representing transient neuronal swelling in gray matter of neocortex, hippocampus, striatum, and thalamus. In contrast, SD Kt was not imaged in hypothalamic nuclei or brainstem with exception of those nuclei near the dorsal brainstem surface. In rat slices, single neurons were whole-cell current clamped during SD Kt. "Higher" neurons depolarized to near zero millivolts indicating SD Kt generation. In contrast, seven types of neurons in hypothalamus and brainstem only slowly depolarized without generating SD Kt, supporting our imaging findings. Therefore, SD Kt is not a default of CNS neurons but rather displays a region-specific susceptibility, similar to anoxic depolarization, which we have proposed is correlated with a region's vulnerability to traumatic brain injury. In the higher brain, SD Kt may be a vestigial spreading depolarization that originally evolved to shut down and vasoconstrict gray matter regions more exposed to impact and contusion.