Dynamic interaction of local and transhemispheric networks is necessary for progressive intensification of hippocampal seizures
Berglind, Fredrik LU ; Andersson, My LU
and Kokaia, Merab
LU
(2018)
In Scientific Reports
8(1).
- Abstract
The detailed mechanisms of progressive intensification of seizures often occurring in epilepsy are not well understood. Animal models of kindling, with progressive intensification of stimulation-induced seizures, have been previously used to investigate alterations in neuronal networks, but has been obscured by limited recording capabilities during electrical stimulations. Remote networks in kindling have been studied by physical deletions of the connected structures or pathways, inevitably leading to structural reorganisations and related adverse effects. We used optogenetics to circumvent the above-mentioned problems inherent to electrical kindling, and chemogenetics to temporarily inhibit rather than ablate the remote interconnected... (More)
The detailed mechanisms of progressive intensification of seizures often occurring in epilepsy are not well understood. Animal models of kindling, with progressive intensification of stimulation-induced seizures, have been previously used to investigate alterations in neuronal networks, but has been obscured by limited recording capabilities during electrical stimulations. Remote networks in kindling have been studied by physical deletions of the connected structures or pathways, inevitably leading to structural reorganisations and related adverse effects. We used optogenetics to circumvent the above-mentioned problems inherent to electrical kindling, and chemogenetics to temporarily inhibit rather than ablate the remote interconnected networks. Progressively intensifying afterdischarges (ADs) were induced by repetitive photoactivation of principal neurons in the hippocampus of anaesthetized transgenic mice expressing ChR2. This allowed, during the stimulation, to reveal dynamic increases in local field potentials (LFPs), which coincided with the start of AD intensification. Furthermore, chemogenetic functional inhibition of contralateral hippocampal neurons via hM4D(Gi) receptors abrogated AD progression. These findings demonstrate that, during repeated activation, local circuits undergo acute plastic changes with appearance of additional network discharges (LFPs), leading to transhemispheric recruitment of contralateral dentate gyrus, which seems to be necessary for progressive intensification of ADs.
(Less)
- author
- Berglind, Fredrik
LU
; Andersson, My
LU
and Kokaia, Merab
LU
- organization
- publishing date
- 2018-12-01
- type
- Contribution to journal
- publication status
- published
- subject
- in
- Scientific Reports
- volume
- 8
- issue
- 1
- article number
- 5669
- publisher
- Nature Publishing Group
- external identifiers
-
- scopus:85044950420
- pmid:29618778
- ISSN
- 2045-2322
- DOI
- 10.1038/s41598-018-23659-x
- language
- English
- LU publication?
- yes
- id
- 105e7e00-2c1d-4f2c-aa5b-221462d7f62c
- date added to LUP
- 2018-04-16 15:23:42
- date last changed
- 2024-04-15 06:35:08
@article{105e7e00-2c1d-4f2c-aa5b-221462d7f62c,
abstract = {{<p>The detailed mechanisms of progressive intensification of seizures often occurring in epilepsy are not well understood. Animal models of kindling, with progressive intensification of stimulation-induced seizures, have been previously used to investigate alterations in neuronal networks, but has been obscured by limited recording capabilities during electrical stimulations. Remote networks in kindling have been studied by physical deletions of the connected structures or pathways, inevitably leading to structural reorganisations and related adverse effects. We used optogenetics to circumvent the above-mentioned problems inherent to electrical kindling, and chemogenetics to temporarily inhibit rather than ablate the remote interconnected networks. Progressively intensifying afterdischarges (ADs) were induced by repetitive photoactivation of principal neurons in the hippocampus of anaesthetized transgenic mice expressing ChR2. This allowed, during the stimulation, to reveal dynamic increases in local field potentials (LFPs), which coincided with the start of AD intensification. Furthermore, chemogenetic functional inhibition of contralateral hippocampal neurons via hM4D(Gi) receptors abrogated AD progression. These findings demonstrate that, during repeated activation, local circuits undergo acute plastic changes with appearance of additional network discharges (LFPs), leading to transhemispheric recruitment of contralateral dentate gyrus, which seems to be necessary for progressive intensification of ADs.</p>}},
author = {{Berglind, Fredrik and Andersson, My and Kokaia, Merab}},
issn = {{2045-2322}},
language = {{eng}},
month = {{12}},
number = {{1}},
publisher = {{Nature Publishing Group}},
series = {{Scientific Reports}},
title = {{Dynamic interaction of local and transhemispheric networks is necessary for progressive intensification of hippocampal seizures}},
url = {{http://dx.doi.org/10.1038/s41598-018-23659-x}},
doi = {{10.1038/s41598-018-23659-x}},
volume = {{8}},
year = {{2018}},
}