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Optogenetic control of epileptiform activity.

Tønnesen, Jan; Toft Sörensen, Andreas LU ; Deisseroth, Karl; Lundberg, Cecilia LU and Kokaia, Merab LU (2009) In Proceedings of the National Academy of Sciences 106(29). p.12162-12167
Abstract
The optogenetic approach to gain control over neuronal excitability both in vitro and in vivo has emerged as a fascinating scientific tool to explore neuronal networks, but it also opens possibilities for developing novel treatment strategies for neurologic conditions. We have explored whether such an optogenetic approach using the light-driven halorhodopsin chloride pump from Natronomonas pharaonis (NpHR), modified for mammalian CNS expression to hyperpolarize central neurons, may inhibit excessive hyperexcitability and epileptiform activity. We show that a lentiviral vector containing the NpHR gene under the calcium/calmodulin-dependent protein kinase IIalpha promoter transduces principal cells of the hippocampus and cortex and... (More)
The optogenetic approach to gain control over neuronal excitability both in vitro and in vivo has emerged as a fascinating scientific tool to explore neuronal networks, but it also opens possibilities for developing novel treatment strategies for neurologic conditions. We have explored whether such an optogenetic approach using the light-driven halorhodopsin chloride pump from Natronomonas pharaonis (NpHR), modified for mammalian CNS expression to hyperpolarize central neurons, may inhibit excessive hyperexcitability and epileptiform activity. We show that a lentiviral vector containing the NpHR gene under the calcium/calmodulin-dependent protein kinase IIalpha promoter transduces principal cells of the hippocampus and cortex and hyperpolarizes these cells, preventing generation of action potentials and epileptiform activity during optical stimulation. This study proves a principle, that selective hyperpolarization of principal cortical neurons by NpHR is sufficient to curtail paroxysmal activity in transduced neurons and can inhibit stimulation train-induced bursting in hippocampal organotypic slice cultures, which represents a model tissue of pharmacoresistant epilepsy. This study demonstrates that the optogenetic approach may prove useful for controlling epileptiform activity and opens a future perspective to develop it into a strategy to treat epilepsy. (Less)
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author
organization
publishing date
type
Contribution to journal
publication status
published
subject
keywords
NpHR, paroxysmal depolarizing shift (PDS), epilepsy, hippocampus, stimulation train-induced bursting (STIB)
in
Proceedings of the National Academy of Sciences
volume
106
issue
29
pages
12162 - 12167
publisher
National Acad Sciences
external identifiers
  • wos:000268178400062
  • pmid:19581573
  • scopus:67749098051
ISSN
1091-6490
DOI
10.1073/pnas.0901915106
language
English
LU publication?
yes
id
70949352-7596-4db2-8a81-cfbee76ad475 (old id 1453373)
alternative location
http://www.ncbi.nlm.nih.gov/pubmed/19581573?dopt=Abstract
date added to LUP
2009-08-04 10:22:43
date last changed
2017-12-10 04:41:51
@article{70949352-7596-4db2-8a81-cfbee76ad475,
  abstract     = {The optogenetic approach to gain control over neuronal excitability both in vitro and in vivo has emerged as a fascinating scientific tool to explore neuronal networks, but it also opens possibilities for developing novel treatment strategies for neurologic conditions. We have explored whether such an optogenetic approach using the light-driven halorhodopsin chloride pump from Natronomonas pharaonis (NpHR), modified for mammalian CNS expression to hyperpolarize central neurons, may inhibit excessive hyperexcitability and epileptiform activity. We show that a lentiviral vector containing the NpHR gene under the calcium/calmodulin-dependent protein kinase IIalpha promoter transduces principal cells of the hippocampus and cortex and hyperpolarizes these cells, preventing generation of action potentials and epileptiform activity during optical stimulation. This study proves a principle, that selective hyperpolarization of principal cortical neurons by NpHR is sufficient to curtail paroxysmal activity in transduced neurons and can inhibit stimulation train-induced bursting in hippocampal organotypic slice cultures, which represents a model tissue of pharmacoresistant epilepsy. This study demonstrates that the optogenetic approach may prove useful for controlling epileptiform activity and opens a future perspective to develop it into a strategy to treat epilepsy.},
  author       = {Tønnesen, Jan and Toft Sörensen, Andreas and Deisseroth, Karl and Lundberg, Cecilia and Kokaia, Merab},
  issn         = {1091-6490},
  keyword      = {NpHR,paroxysmal depolarizing shift (PDS),epilepsy,hippocampus,stimulation train-induced bursting (STIB)},
  language     = {eng},
  number       = {29},
  pages        = {12162--12167},
  publisher    = {National Acad Sciences},
  series       = {Proceedings of the National Academy of Sciences},
  title        = {Optogenetic control of epileptiform activity.},
  url          = {http://dx.doi.org/10.1073/pnas.0901915106},
  volume       = {106},
  year         = {2009},
}