Functional neuroplasticity in the nucleus tractus solitarius and increased risk of sudden death in mice with acquired temporal lobe epilepsy

Isabel D. Derera, Brian P. Delisle, Bret N. Smith

Research output: Contribution to journalArticlepeer-review

17 Scopus citations

Abstract

Sudden unexpected death in epilepsy (SUDEP) is the leading cause of death in individuals with refractory acquired epilepsy. Cardiorespiratory failure is the most likely cause in most cases, and central autonomic dysfunction has been implicated as a contributing factor to SUDEP. Neurons of the nucleus tractus solitarius (NTS) in the brainstem vagal complex receive and integrate vagally mediated information regarding cardiorespiratory and other autonomic functions, and GABAergic inhibitory NTS neurons play an essential role in modulating autonomic output. We assessed the activity of GABAergic NTS neurons as a function of epilepsy development in the pilocarpine-induced status epilepticus (SE) model of temporal lobe epilepsy (TLE). Compared with agematched controls, mice that survived SE had significantly lower survival rates by 150 d post-SE. GABAergic NTS neurons from mice that survived SE displayed a glutamate-dependent increase in spontaneous action potential firing rate by 12 wks post-SE. Increased spontaneous EPSC frequency was also detected, but vagal afferent synaptic release properties were unaltered, suggesting that an increase in glutamate release from central neurons developed in the NTS after SE. Our results indicate that long-term changes in glutamate release and activity of GABAergic neurons emerge in the NTS in association with epileptogenesis. These changes might contribute to increased risk of cardiorespiratory dysfunction and sudden death in this model of TLE.

Original languageEnglish
Article numbere0319-17.2017
JournaleNeuro
Volume4
Issue number5
DOIs
StatePublished - Sep 1 2017

Bibliographical note

Publisher Copyright:
© 2017 Derera et al.

Keywords

  • Autonomic
  • Brainstem
  • EPSC
  • Epilepsy
  • GABA
  • Vagus

ASJC Scopus subject areas

  • General Neuroscience

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