Evolving Concepts on the Pathophysiology of Absence Seizures

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

“…In this manner we ruled out the possibility that the spatial restriction of activity was due to an anatomical disconnect. These results suggest that when both anatomical structures are simultaneously exposed to the same condition of perturbed excitation and inhibition, neocortex is the site of focal seizure onset in the TC system, consistent with previous reports (Coulter and Lee, 1993; Meeren et al, 2005; Gigout et al, 2013). …”

“…Our data indicating a dominant role for cortex in seizure generation in the TC system is consistent with previous reports that employed a variety of epilepsy studies, including ionic, pharmacological, and genetic models, examined both in vitro (Coulter and Lee, 1993; Gigout et al, 2013) and in vivo (Steriade and Contreras, 1998; Meeren et al, 2002; Coenen and Van Luijtelaar, 2003; Meeren et al, 2005). The consistency of this result in many different model systems strongly suggests that neocortex has an intrinsic predisposition for seizure generation.…”

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

“…In this manner we ruled out the possibility that the spatial restriction of activity was due to an anatomical disconnect. These results suggest that when both anatomical structures are simultaneously exposed to the same condition of perturbed excitation and inhibition, neocortex is the site of focal seizure onset in the TC system, consistent with previous reports (Coulter and Lee, 1993; Meeren et al, 2005; Gigout et al, 2013). …”

“…Our data indicating a dominant role for cortex in seizure generation in the TC system is consistent with previous reports that employed a variety of epilepsy studies, including ionic, pharmacological, and genetic models, examined both in vitro (Coulter and Lee, 1993; Gigout et al, 2013) and in vivo (Steriade and Contreras, 1998; Meeren et al, 2002; Coenen and Van Luijtelaar, 2003; Meeren et al, 2005). The consistency of this result in many different model systems strongly suggests that neocortex has an intrinsic predisposition for seizure generation.…”

Glutamatergic alterations in the cortex of genetic absence epilepsy rats

“…The present work provides biochemical data suggesting an alteration in GLU transmission, restricted to the cortex of GAERS. These data are in accordance with previous studies demonstrating: a) a primary role of corticothalamic neurons in the synchronized excitation of thalamic relay and reticular neurons in GAERS [ 13 ], b) initiation of the paroxysmal oscillation by a cortical focus in WAG/Rij rats, another model of absence epilepsy [ 14 ], and, c) immediate cessation of SWD on applying the anti-absence drug, ethosuximide, to a focalized zone in the cortex, but not the thalamus, in GAERS [ 15 ].…”

Cortical Glutamate Metabolism is Enhanced in a Genetic Model of Absence Epilepsy

“…This dysregulation leads to impaired thalamic filter function and hence reduced sensory input to the cortex allowing the occurrence of SWDs in the thalamocortical loop. This is in good agreement with the recent hypothesis that SWDs are driven by a cortical focus (Meeren et al , 2002, 2005). Likewise, increased glutamatergic output from the cortex to hippocampus may be the underlying cause of improved learning in GAERS.…”

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

“…In this manner we ruled out the possibility that the spatial restriction of activity was due to an anatomical disconnect. These results suggest that when both anatomical structures are simultaneously exposed to the same condition of perturbed excitation and inhibition, neocortex is the site of focal seizure onset in the TC system, consistent with previous reports (Coulter and Lee, 1993; Meeren et al, 2005; Gigout et al, 2013). …”

“…Our data indicating a dominant role for cortex in seizure generation in the TC system is consistent with previous reports that employed a variety of epilepsy studies, including ionic, pharmacological, and genetic models, examined both in vitro (Coulter and Lee, 1993; Gigout et al, 2013) and in vivo (Steriade and Contreras, 1998; Meeren et al, 2002; Coenen and Van Luijtelaar, 2003; Meeren et al, 2005). The consistency of this result in many different model systems strongly suggests that neocortex has an intrinsic predisposition for seizure generation.…”

Glutamatergic alterations in the cortex of genetic absence epilepsy rats

“…The present work provides biochemical data suggesting an alteration in GLU transmission, restricted to the cortex of GAERS. These data are in accordance with previous studies demonstrating: a) a primary role of corticothalamic neurons in the synchronized excitation of thalamic relay and reticular neurons in GAERS [ 13 ], b) initiation of the paroxysmal oscillation by a cortical focus in WAG/Rij rats, another model of absence epilepsy [ 14 ], and, c) immediate cessation of SWD on applying the anti-absence drug, ethosuximide, to a focalized zone in the cortex, but not the thalamus, in GAERS [ 15 ].…”

Cortical Glutamate Metabolism is Enhanced in a Genetic Model of Absence Epilepsy

“…This dysregulation leads to impaired thalamic filter function and hence reduced sensory input to the cortex allowing the occurrence of SWDs in the thalamocortical loop. This is in good agreement with the recent hypothesis that SWDs are driven by a cortical focus (Meeren et al , 2002, 2005). Likewise, increased glutamatergic output from the cortex to hippocampus may be the underlying cause of improved learning in GAERS.…”

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

“…In this manner we ruled out the possibility that the spatial restriction of activity was due to an anatomical disconnect. These results suggest that when both anatomical structures are simultaneously exposed to the same condition of perturbed excitation and inhibition, neocortex is the site of focal seizure onset in the TC system, consistent with previous reports (Coulter and Lee, 1993; Meeren et al, 2005; Gigout et al, 2013). …”

“…Our data indicating a dominant role for cortex in seizure generation in the TC system is consistent with previous reports that employed a variety of epilepsy studies, including ionic, pharmacological, and genetic models, examined both in vitro (Coulter and Lee, 1993; Gigout et al, 2013) and in vivo (Steriade and Contreras, 1998; Meeren et al, 2002; Coenen and Van Luijtelaar, 2003; Meeren et al, 2005). The consistency of this result in many different model systems strongly suggests that neocortex has an intrinsic predisposition for seizure generation.…”

Glutamatergic alterations in the cortex of genetic absence epilepsy rats

“…The present work provides biochemical data suggesting an alteration in GLU transmission, restricted to the cortex of GAERS. These data are in accordance with previous studies demonstrating: a) a primary role of corticothalamic neurons in the synchronized excitation of thalamic relay and reticular neurons in GAERS [ 13 ], b) initiation of the paroxysmal oscillation by a cortical focus in WAG/Rij rats, another model of absence epilepsy [ 14 ], and, c) immediate cessation of SWD on applying the anti-absence drug, ethosuximide, to a focalized zone in the cortex, but not the thalamus, in GAERS [ 15 ].…”

Cortical Glutamate Metabolism is Enhanced in a Genetic Model of Absence Epilepsy

“…This dysregulation leads to impaired thalamic filter function and hence reduced sensory input to the cortex allowing the occurrence of SWDs in the thalamocortical loop. This is in good agreement with the recent hypothesis that SWDs are driven by a cortical focus (Meeren et al , 2002, 2005). Likewise, increased glutamatergic output from the cortex to hippocampus may be the underlying cause of improved learning in GAERS.…”