Chemically activated luminopsins allow optogenetic inhibition of distributed nodes in an epileptic network for non-invasive and multi-site suppression of seizure activity

• Type of Material: Article
• Authors: Jack K. Tung, Georgia Institute of Technology; Fu Hung Shiu, Emory University; Kevin Ding, Emory University; Robert Gross, Emory University
• Language: English
• Date: 2018-01-01
• Publisher: Elsevier: 12 months
• Publication Version: Author Accepted Manuscript (After Peer Review)
• Copyright Statement: © 2017 Elsevier Inc.
• License: Creative Commons Attribution-NonCommercial-NoDerivs 4.0 International
• Final Published Version (URL): http://dx.doi.org/10.1016/j.nbd.2017.09.007
• Title of Journal or Parent Work: Neurobiology of Disease
• ISSN: 0969-9961
• Volume: 109
• Issue: Pt A
• Start Page: 1
• End Page: 10
• Grant/Funding Information: NS079268 and NS079757 to R.E.G., NS086433 to J.K.T.
• Keywords: Neurosciences & Neurology; ANTERIOR NUCLEUS; THALAMUS; Circuits; ELECTRICAL-STIMULATION; CORTEX; EPILEPSIES; RAT; Luminopsin; DENTATE GYRUS; NEURAL CIRCUITS; DEEP BRAIN-STIMULATION; Science & Technology; Optogenetics; Networks; Epilepsy; Life Sciences & Biomedicine; Neurosciences
• Research Categories: Biology, Neuroscience; Engineering, Biomedical; Health Sciences, Medicine and Surgery

Abstract

Although optogenetic techniques have proven to be invaluable for manipulating and understanding complex neural dynamics over the past decade, they still face practical and translational challenges in targeting networks involving multiple, large, or difficult-to-illuminate areas of the brain. We utilized inhibitory luminopsins to simultaneously inhibit the dentate gyrus and anterior nucleus of the thalamus of the rat brain in a hardware-independent and cell-type specific manner. This approach was more effective at suppressing behavioral seizures than inhibition of the individual structures in a rat model of epilepsy. In addition to elucidating mechanisms of seizure suppression never directly demonstrated before, this work also illustrates how precise multi-focal control of pathological circuits can be advantageous for the treatment and understanding of disorders involving broad neural circuits such as epilepsy.