Increased excitability and excitatory synaptic transmission during in vitro ischemia in the neonatal mouse hippocampus

S. A. Zanelli, K. Rajasekaran, D. K. Grosenbaugh, J. Kapur

Research output: Contribution to journalArticlepeer-review

17 Scopus citations

Abstract

Objective: The present study tested the hypothesis that exposure to in vitro hypoxia-ischemia alters membrane properties and excitability as well as excitatory synaptic transmission of CA1 pyramidal neurons in the neonatal mouse. Methods: Experiments were conducted in hippocampal slices in P7-P9 C57Bl/6 mice using whole-cell patch clamp in current- and voltage-clamp mode. Passive membrane potential (Vm), input resistance (Rin) and active (action potential (AP) threshold and amplitude) membrane properties of CA1 pyramidal neurons were assessed at baseline, during 10min in vitro ischemia (oxygen-glucose deprivation (OGD)) and during reoxygenation. Spontaneous and miniature excitatory post-synaptic currents (s and mEPSCs) were studied under similar conditions. Results: OGD caused significant depolarization of CA1 pyramidal neurons as well as decrease in AP threshold and increase in AP amplitude. These changes were blocked by the application of tetrodotoxin (TTX), indicating Na+ channels' involvement. Following 10min of reoxygenation, significant membrane hyperpolarization was noted and it was associated with a decrease in Rin. AP threshold and amplitude returned to baseline during that stage. sEPSC and mEPSC frequency increased during both OGD and reoxygenation but their amplitude remained unchanged. Additionally, we found that OGD decreases Ih (hyperpolarization activated current) in CA1 neurons from neonatal mice and this effect persists during reoxygenation. Significance: These results indicate that in vitro ischemia leads to changes in membrane excitability mediated by sodium and potassium channels. Further, it results in enhanced neurotransmitter release from presynaptic terminals. These changes are likely to represent one of the mechanisms of hypoxia/ischemia-mediated seizures in the neonatal period.

Original languageEnglish (US)
Pages (from-to)279-289
Number of pages11
JournalNeuroscience
Volume310
DOIs
StatePublished - Dec 3 2015

Keywords

  • Electrophysiology
  • Excitability
  • Excitatory postsynaptic current
  • Neonatal brain
  • Seizure

ASJC Scopus subject areas

  • Neuroscience(all)

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