Dynamic gain analysis reveals encoding deficiencies in cortical neurons that recover from hypoxia-induced spreading depolarizations

Omer Revah, Ohad Stoler, Andreas Neef, Fred Wolf, Ilya A. Fleidervish, Michael J. Gutnick

Research output: Contribution to journalArticlepeer-review

11 Scopus citations


Cortical regions that are damaged by insults, such as ischemia, hypoxia, and trauma, frequently generate spreading depolarization (SD). At the neuronal level, SDs entail complete breakdown of ionic gradients, persisting for seconds to minutes. It is unclear whether these transient events have a more lasting influence on neuronal function. Here, we describe electrophysiological changes in cortical neurons after recovery from hypoxia-induced SD. When examined with standard measures of neuronal excitability several hours after recovery from SD, layer 5 pyramidal neurons in brain slices from mice of either sex appear surprisingly normal. However, we here introduce an additional parameter, dynamic gain, which characterizes the bandwidth of action potential encoding by a neuron, and thereby reflects its potential efficiency in a multineuronal circuit. We find that the ability of neurons that recover from SD to track high-frequency inputs is markedly curtailed; exposure to hypoxia did not have this effect when SD was prevented pharmacologically. Staining for Ankyrin G revealed at least a fourfold decrease in the number of intact axon initial segments in post-SD slices. Since this effect, along with the effect on encoding, was blocked by an inhibitor of the Ca 2+-dependent enzyme, calpain, we conclude that both effects were mediated by the SD-induced rise in intracellular Ca 2+. Although effects of calpain activation were detected in the axon initial segment, changes in soma-dendritic compartments may also be involved. Whatever the precise molecular mechanism, our findings indicate that in the context of cortical circuit function, effectiveness of neurons that survive SD may be limited.

Original languageEnglish
Pages (from-to)7790-7800
Number of pages11
JournalJournal of Neuroscience
Issue number39
StatePublished - 25 Sep 2019


  • Axon initial segment
  • Calpain
  • Cortex
  • Layer 5 pyramidal neurons
  • Neuronal encoding
  • Spreading depolarization

ASJC Scopus subject areas

  • General Neuroscience


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