Optogenetic inhibition of chemically induced hypersynchronized bursting in mice

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

N1 - Copyright © 2014 Elsevier Inc. All rights reserved.

PY - 2014/5

Y1 - 2014/5

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.

KW - Action Potentials

KW - Aminopyridines

KW - Analysis of Variance

KW - Animals

KW - Bacterial Proteins

KW - Disease Models, Animal

KW - Excitatory Amino Acid Agonists

KW - Female

KW - GABA Agents

KW - GABA Antagonists

KW - Halorhodopsins

KW - In Vitro Techniques

KW - Kainic Acid

KW - Luminescent Proteins

KW - Membrane Potentials

KW - Mice

KW - Neurons

KW - Optogenetics

KW - Patch-Clamp Techniques

KW - Picrotoxin

KW - Status Epilepticus

KW - Transduction, Genetic

KW - Journal Article

KW - Research Support, Non-U.S. Gov't

U2 - 10.1016/j.nbd.2014.01.015

DO - 10.1016/j.nbd.2014.01.015

M3 - Journal article

C2 - 24491965

SN - 0969-9961

VL - 65

SP - 133

EP - 141

JO - Neurobiology of Disease

JF - Neurobiology of Disease

ER -