Skip to main content

Lund University Publications

LUND UNIVERSITY LIBRARIES

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

Wickham, J LU orcid ; Ledri, M LU ; Andersson, M LU orcid and Kokaia, M LU (2023) In Cerebral Cortex 33(10). p.6171-6183
Abstract

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... (More)

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.

(Less)
Please use this url to cite or link to this publication:
author
; ; and
organization
publishing date
type
Contribution to journal
publication status
published
subject
in
Cerebral Cortex
volume
33
issue
10
pages
6171 - 6183
publisher
Oxford University Press
external identifiers
  • scopus:85161688661
  • pmid:36611229
ISSN
1460-2199
DOI
10.1093/cercor/bhac493
language
English
LU publication?
yes
additional info
© The Author(s) 2023. Published by Oxford University Press. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.
id
efb0333f-d00a-43ac-8609-d76e5e08afc2
date added to LUP
2023-03-06 09:13:54
date last changed
2024-06-15 07:42:44
@article{efb0333f-d00a-43ac-8609-d76e5e08afc2,
  abstract     = {{<p>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.</p>}},
  author       = {{Wickham, J and Ledri, M and Andersson, M and Kokaia, M}},
  issn         = {{1460-2199}},
  language     = {{eng}},
  month        = {{01}},
  number       = {{10}},
  pages        = {{6171--6183}},
  publisher    = {{Oxford University Press}},
  series       = {{Cerebral Cortex}},
  title        = {{Cell-specific switch for epileptiform activity : critical role of interneurons in the mouse subicular network}},
  url          = {{http://dx.doi.org/10.1093/cercor/bhac493}},
  doi          = {{10.1093/cercor/bhac493}},
  volume       = {{33}},
  year         = {{2023}},
}