title: Bidirectional Control of Generalized Epilepsy Networks via Rapid Real-Time Switching of Firing Mode.
abstract: Thalamic relay neurons have well-characterized dual firing modes: bursting and tonic spiking. Studies in brain slices have led to a model in which rhythmic synchronized spiking (phasic firing) in a population of relay neurons leads to hyper-synchronous oscillatory cortico-thalamo-cortical rhythms that result in absence seizures. This model suggests that blocking thalamocortical phasic firing would treat absence seizures. However, recent in vivo studies in anesthetized animals have questioned this simple model. Here we resolve this issue by developing a real-time, mode-switching approach to drive thalamocortical neurons into or out of a phasic firing mode in two freely behaving genetic rodent models of absence epilepsy. Toggling between phasic and tonic firing in thalamocortical neurons launched and aborted absence seizures, respectively. Thus, a synchronous thalamocortical phasic firing state is required for absence seizures, and switching to tonic firing rapidly halts absences. This approach should be useful for modulating other networks that have mode-dependent behaviors.
authors.affiliation: Stanford Neurosciences Graduate Training Program, Stanford University, Stanford, CA 94305, USA; Department of Neurology and Neurological Sciences, Stanford University School of Medicine, Stanford, CA 94305, USA.
authors.forename: Jordan M
authors.initials: JM
authors.lastname: Sorokin
authors.affiliation: Howard Hughes Medical Institute and Center for Integrative Neuroscience, University of California San Francisco, San Francisco, CA 94158, USA.
authors.forename: Thomas J
authors.initials: TJ
authors.lastname: Davidson
authors.affiliation: Department of Neurology and Neurological Sciences, Stanford University School of Medicine, Stanford, CA 94305, USA.
authors.forename: Eric
authors.initials: E
authors.lastname: Frechette
authors.affiliation: Department of Neurology and Neurological Sciences, Stanford University School of Medicine, Stanford, CA 94305, USA.
authors.forename: Armen M
authors.initials: AM
authors.lastname: Abramian
authors.affiliation: Department of Bioengineering, Stanford University School of Medicine, Stanford, CA 94305, USA.
authors.forename: Karl
authors.initials: K
authors.lastname: Deisseroth
authors.affiliation: Department of Neurology and Neurological Sciences, Stanford University School of Medicine, Stanford, CA 94305, USA.
authors.forename: John R
authors.initials: JR
authors.lastname: Huguenard
authors.affiliation: Gladstone Institutes, San Francisco, CA 94158, USA; Department of Neurology, University of California San Francisco, San Francisco, CA 94158, USA. Electronic address: jeanne.paz@gladstone.ucsf.edu.
authors.forename: Jeanne T
authors.initials: JT
authors.lastname: Paz
mesh_terms: D000818:Animals; D058256:Brain Waves; D002540:Cerebral Cortex / Q000166:cytology / Q000503:physiopathology*; D004195:Disease Models, Animal; D000069280:Electrocorticography; D004827:Epilepsy / Q000503:physiopathology; D004832:Epilepsy, Absence / Q000503:physiopathology*; D051379:Mice; D009415:Nerve Net / Q000503:physiopathology*; D009434:Neural Pathways; D009474:Neurons / Q000502:physiology*; D062308:Optogenetics; D018408:Patch-Clamp Techniques; D051381:Rats; D013788:Thalamus / Q000166:cytology / Q000503:physiopathology*
keywords: SSFO; bursts; closed-loop; electrophysiology; epilepsy; optogenetics; oscillations; thalamocortical