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Optogenetic inhibition of chemically induced hypersynchronized bursting in mice.

Berglind, Fredrik LU ; Ledri, Marco LU ; Sørensen, Andreas Toft; Nikitidou, Litsa LU ; Melis, Miriam LU ; Bielefeld, Pascal LU ; Kirik, Deniz LU ; Deisseroth, Karl; Andersson, My LU and Kokaia, Merab LU (2014) In Neurobiology of Disease 65. p.133-141
Abstract
Synchronized activity is common during various physiological operations but can culminate in seizures and consequently in epilepsy in pathological hyperexcitable conditions in the brain. Many types of seizures are not possible to control and impose significant disability for patients with epilepsy. Such intractable epilepsy cases are often associated with degeneration of inhibitory interneurons in the cortical areas resulting in impaired inhibitory drive onto the principal neurons. Recently emerging optogenetic technique has been proposed as an alternative approach to control such seizures but whether it may be effective in situations where inhibitory processes in the brain are compromised has not been addressed. Here we used... (More)
Synchronized activity is common during various physiological operations but can culminate in seizures and consequently in epilepsy in pathological hyperexcitable conditions in the brain. Many types of seizures are not possible to control and impose significant disability for patients with epilepsy. Such intractable epilepsy cases are often associated with degeneration of inhibitory interneurons in the cortical areas resulting in impaired inhibitory drive onto the principal neurons. Recently emerging optogenetic technique has been proposed as an alternative approach to control such seizures but whether it may be effective in situations where inhibitory processes in the brain are compromised has not been addressed. Here we used pharmacological and optogenetic techniques to block inhibitory neurotransmission and induce epileptiform activity in vitro and in vivo. We demonstrate that NpHR-based optogenetic hyperpolarization and thereby inactivation of a principal neuronal population in the hippocampus is effectively attenuating seizure activity caused by disconnected network inhibition both in vitro and in vivo. Our data suggest that epileptiform activity in the hippocampus caused by impaired inhibition may be controlled by optogenetic silencing of principal neurons and potentially can be developed as an alternative treatment for epilepsy. (Less)
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author
organization
publishing date
type
Contribution to journal
publication status
published
subject
in
Neurobiology of Disease
volume
65
pages
133 - 141
publisher
Elsevier
external identifiers
  • pmid:24491965
  • wos:000333546300013
  • scopus:84894236025
ISSN
0969-9961
DOI
10.1016/j.nbd.2014.01.015
language
English
LU publication?
yes
id
6498d2d4-c40b-42dc-9310-7fa9b03838a2 (old id 4335726)
alternative location
http://www.ncbi.nlm.nih.gov/pubmed/24491965?dopt=Abstract
date added to LUP
2014-03-06 22:42:33
date last changed
2017-11-05 03:04:00
@article{6498d2d4-c40b-42dc-9310-7fa9b03838a2,
  abstract     = {Synchronized activity is common during various physiological operations but can culminate in seizures and consequently in epilepsy in pathological hyperexcitable conditions in the brain. Many types of seizures are not possible to control and impose significant disability for patients with epilepsy. Such intractable epilepsy cases are often associated with degeneration of inhibitory interneurons in the cortical areas resulting in impaired inhibitory drive onto the principal neurons. Recently emerging optogenetic technique has been proposed as an alternative approach to control such seizures but whether it may be effective in situations where inhibitory processes in the brain are compromised has not been addressed. Here we used pharmacological and optogenetic techniques to block inhibitory neurotransmission and induce epileptiform activity in vitro and in vivo. We demonstrate that NpHR-based optogenetic hyperpolarization and thereby inactivation of a principal neuronal population in the hippocampus is effectively attenuating seizure activity caused by disconnected network inhibition both in vitro and in vivo. Our data suggest that epileptiform activity in the hippocampus caused by impaired inhibition may be controlled by optogenetic silencing of principal neurons and potentially can be developed as an alternative treatment for epilepsy.},
  author       = {Berglind, Fredrik and Ledri, Marco and Sørensen, Andreas Toft and Nikitidou, Litsa and Melis, Miriam and Bielefeld, Pascal and Kirik, Deniz and Deisseroth, Karl and Andersson, My and Kokaia, Merab},
  issn         = {0969-9961},
  language     = {eng},
  pages        = {133--141},
  publisher    = {Elsevier},
  series       = {Neurobiology of Disease},
  title        = {Optogenetic inhibition of chemically induced hypersynchronized bursting in mice.},
  url          = {http://dx.doi.org/10.1016/j.nbd.2014.01.015},
  volume       = {65},
  year         = {2014},
}