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 age-matched 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.

Document Type

Article

Publication Date

10-23-2017

Notes/Citation Information

Published in eNeuro, v. 4, issue 5, p. 1-13.

© 2017 Derera et al.

This is an open-access article distributed under the terms of the Creative Commons Attribution 4.0 International license, which permits unrestricted use, distribution and reproduction in any medium provided that the original work is properly attributed.

Digital Object Identifier (DOI)

https://doi.org/10.1523/ENEURO.0319-17.2017

Funding Information

This work was funded by NIH R21 NS 088608; NIH R01 DK056132; UK Epilepsy Center.

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