title: Local changes in neocortical circuit dynamics coincide with the spread of seizures to thalamus in a model of epilepsy.
abstract: During the generalization of epileptic seizures, pathological activity in one brain area recruits distant brain structures into joint synchronous discharges. However, it remains unknown whether specific changes in local circuit activity are related to the aberrant recruitment of anatomically distant structures into epileptiform discharges. Further, it is not known whether aberrant areas recruit or entrain healthy ones into pathological activity. Here we study the dynamics of local circuit activity during the spread of epileptiform discharges in the zero-magnesium in vitro model of epilepsy. We employ high-speed multi-photon imaging in combination with dual whole-cell recordings in acute thalamocortical (TC) slices of the juvenile mouse to characterize the generalization of epileptic activity between neocortex and thalamus. We find that, although both structures are exposed to zero-magnesium, the initial onset of focal epileptiform discharge occurs in cortex. This suggests that local recurrent connectivity that is particularly prevalent in cortex is important for the initiation of seizure activity. Subsequent recruitment of thalamus into joint, generalized discharges is coincident with an increase in the coherence of local cortical circuit activity that itself does not depend on thalamus. Finally, the intensity of population discharges is positively correlated between both brain areas. This suggests that during and after seizure generalization not only the timing but also the amplitude of epileptiform discharges in thalamus is entrained by cortex. Together these results suggest a central role of neocortical activity for the onset and the structure of pathological recruitment of thalamus into joint synchronous epileptiform discharges.
authors.affiliation: Department of Neurobiology, The University of Chicago Chicago, IL, USA ; Department of Physiology, University of Bern Bern, Switzerland.
authors.forename: Florian B
authors.initials: FB
authors.lastname: Neubauer
authors.affiliation: Department of Neurobiology, The University of Chicago Chicago, IL, USA.
authors.forename: Audrey
authors.initials: A
authors.lastname: Sederberg
authors.affiliation: Department of Neurobiology, The University of Chicago Chicago, IL, USA ; Committee on Computational Neuroscience, The University of Chicago Chicago, IL, USA.
authors.forename: Jason N
authors.initials: JN
authors.lastname: MacLean
mesh_terms: D000200:Action Potentials; D000818:Animals; D000831:Animals, Newborn; D004195:Disease Models, Animal; D004558:Electric Stimulation; D004827:Epilepsy / Q000473:pathology* / Q000503:physiopathology; D066298:In Vitro Techniques; D051379:Mice; D008810:Mice, Inbred C57BL; D019579:Neocortex / Q000503:physiopathology*; D009415:Nerve Net / Q000503:physiopathology*; D009434:Neural Pathways / Q000502:physiology / Q000503:physiopathology; D009474:Neurons / Q000502:physiology*; D018408:Patch-Clamp Techniques; D013788:Thalamus / Q000473:pathology*
keywords: epilepsy model; mouse; neocortex; patch-clamp; seizure generalization; thalamus; two-photon imaging