Cell-specific switch for epileptiform activity: critical role of interneurons in the mouse subicular network

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Sammanfattning

During epileptic seizures, neuronal network activity is hyper synchronized whereby GABAergic parvalbumin-interneurons may have a key role. Previous studies have mostly utilized 4-aminopyridine to induce epileptiform discharges in brain slices from healthy animals. However, it is not clear if the seizure-triggering ability of parvalbumin-interneurons also holds true without the use of external convulsive agents. Here, we investigate whether synchronized activation of parvalbumin-interneurons or principal cells can elicit epileptiform discharges in subiculum slices of epileptic mice. We found that selective synchronized activation of parvalbumin-interneurons or principal cells with optogenetics do not result in light-induced epileptiform discharges (LIEDs) neither in epileptic nor in normal brain slices. Adding 4-aminopyridine to slices, activation of parvalbumin-interneurons still failed to trigger LIEDs. In contrast, such activation of principal neurons readily generated LIEDs with features resembling afterdischarges. When GABAA receptor blocker was added to the perfusion medium, the LIEDs were abolished. These results demonstrate that in subiculum, selective synchronized activation of principal excitatory neurons can trigger epileptiform discharges by recruiting a large pool of downstream interneurons. This study also suggests region-specific role of principal neurons and interneurons in ictogenesis, opening towards differential targeting of specific brain areas for future treatment strategies tailored for individual patients with epilepsy.

Originalspråkengelska
Sidor (från-till)6171-6183
TidskriftCerebral Cortex
Volym33
Nummer10
Tidigt onlinedatum2023 jan. 5
DOI
StatusPublished - 2023

Bibliografisk information

© The Author(s) 2023. Published by Oxford University Press. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

Ämnesklassifikation (UKÄ)

  • Neurovetenskaper

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