Optogenetic inhibition of chemically induced hypersynchronized bursting in mice.

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Optogenetic inhibition of chemically induced hypersynchronized bursting in mice. / Berglind, Fredrik; Ledri, Marco; Sørensen, Andreas Toft; Nikitidou, Litsa; Melis, Miriam; Bielefeld, Pascal; Kirik, Deniz; Deisseroth, Karl; Andersson, My; Kokaia, Merab.

In: Neurobiology of Disease, Vol. 65, 2014, p. 133-141.

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Berglind, Fredrik ; Ledri, Marco ; Sørensen, Andreas Toft ; Nikitidou, Litsa ; Melis, Miriam ; Bielefeld, Pascal ; Kirik, Deniz ; Deisseroth, Karl ; Andersson, My ; Kokaia, Merab. / Optogenetic inhibition of chemically induced hypersynchronized bursting in mice. In: Neurobiology of Disease. 2014 ; Vol. 65. pp. 133-141.

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TY - JOUR

T1 - Optogenetic inhibition of chemically induced hypersynchronized bursting in mice.

AU - Berglind, Fredrik

AU - Ledri, Marco

AU - Sørensen, Andreas Toft

AU - Nikitidou, Litsa

AU - Melis, Miriam

AU - Bielefeld, Pascal

AU - Kirik, Deniz

AU - Deisseroth, Karl

AU - Andersson, My

AU - Kokaia, Merab

PY - 2014

Y1 - 2014

N2 - 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.

AB - 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.

U2 - 10.1016/j.nbd.2014.01.015

DO - 10.1016/j.nbd.2014.01.015

M3 - Article

C2 - 24491965

VL - 65

SP - 133

EP - 141

JO - Neurobiology of Disease

JF - Neurobiology of Disease

SN - 0969-9961

ER -