Local changes in neocortical circuit dynamics coincide with the spread of seizures to thalamus in a model of epilepsy

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...

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Main Authors: Florian B Neubauer, Audrey eSederberg, Jason N MacLean
Format: Article
Language:English
Published: Frontiers Media S.A. 2014-09-01
Series:Frontiers in Neural Circuits
Subjects:
Online Access:http://journal.frontiersin.org/Journal/10.3389/fncir.2014.00101/full
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author Florian B Neubauer
Florian B Neubauer
Audrey eSederberg
Jason N MacLean
Jason N MacLean
author_facet Florian B Neubauer
Florian B Neubauer
Audrey eSederberg
Jason N MacLean
Jason N MacLean
author_sort Florian B Neubauer
collection DOAJ
description 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 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.
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spelling doaj.art-915feab532294c0e89f0d7eac3a26b602022-12-22T02:18:26ZengFrontiers Media S.A.Frontiers in Neural Circuits1662-51102014-09-01810.3389/fncir.2014.00101100212Local changes in neocortical circuit dynamics coincide with the spread of seizures to thalamus in a model of epilepsyFlorian B Neubauer0Florian B Neubauer1Audrey eSederberg2Jason N MacLean3Jason N MacLean4The University of ChicagoUniversity of BernThe University of ChicagoThe University of ChicagoThe University of ChicagoDuring 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 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.http://journal.frontiersin.org/Journal/10.3389/fncir.2014.00101/fullNeocortexThalamusMousepatch-clamptwo-photon imagingepilepsy model
spellingShingle Florian B Neubauer
Florian B Neubauer
Audrey eSederberg
Jason N MacLean
Jason N MacLean
Local changes in neocortical circuit dynamics coincide with the spread of seizures to thalamus in a model of epilepsy
Frontiers in Neural Circuits
Neocortex
Thalamus
Mouse
patch-clamp
two-photon imaging
epilepsy model
title Local changes in neocortical circuit dynamics coincide with the spread of seizures to thalamus in a model of epilepsy
title_full Local changes in neocortical circuit dynamics coincide with the spread of seizures to thalamus in a model of epilepsy
title_fullStr Local changes in neocortical circuit dynamics coincide with the spread of seizures to thalamus in a model of epilepsy
title_full_unstemmed Local changes in neocortical circuit dynamics coincide with the spread of seizures to thalamus in a model of epilepsy
title_short Local changes in neocortical circuit dynamics coincide with the spread of seizures to thalamus in a model of epilepsy
title_sort local changes in neocortical circuit dynamics coincide with the spread of seizures to thalamus in a model of epilepsy
topic Neocortex
Thalamus
Mouse
patch-clamp
two-photon imaging
epilepsy model
url http://journal.frontiersin.org/Journal/10.3389/fncir.2014.00101/full
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