Inhibition of the substantia nigra suppresses absences and clonic seizures in audiogenic rats, but not tonic seizures: evidence for seizure specificity of the nigral control

Deransart, Colin; Lê-Pham, Bich-Thuy; Hirsch, Édouard; Marescaux, C.; Depaulis, Antoine

doi:10.1016/s0306-4522(01)00165-8

Cited by 73 publications

(37 citation statements)

References 41 publications

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“…These data are consistent with the antiepileptic effects of intranigral injections of GABA A agonists or NMDA antagonists in the GAERS SNr (Depaulis et al, 1988(Depaulis et al, , 1989Deransart et al, 1996Deransart et al, , 1998Deransart et al, , 2001) and the aggravation of absence seizures induced by application of GABA A antagonist in the SNr . Changes in the output of STN neurons associated with cortical SWDs could, therefore, provide a subcortical mechanism participating in the control of the abnormal oscillations in the thalamocortical loop.…”

Section: Pathophysiologysupporting

confidence: 86%

Rhythmic Bursting in the Cortico-Subthalamo-Pallidal Network during Spontaneous Genetically Determined Spike and Wave Discharges

Paz¹,

Deniau²,

Charpier³

2005

J. Neurosci.

110

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Absence seizures are characterized by impairment of consciousness associated with bilaterally synchronous spike-and-wave discharges (SWDs) in the electroencephalogram (EEG), which reflect paroxysmal oscillations in thalamocortical networks. Although recent studies suggest that the subthalamic nucleus (STN) provides an endogenous control system that influences the occurrence of absence seizures, the mechanisms of propagation of cortical epileptic discharges in the STN have never been explored. The present study provides the first description of the electrophysiological activity in the cortico-subthalamo-pallidal network during absence seizures in the genetic absence epilepsy rats from Strasbourg, a well established model of absence epilepsy. In corticosubthalamic neurons, the SWDs were associated with repetitive suprathreshold depolarizations correlated with EEG spikes. These cortical paroxysms were reflected in the STN by synchronized, rhythmic, high-frequency bursts of action potentials. Intracellular recordings revealed that the intraburst pattern in STN neurons was sculpted by an early depolarizing synaptic potential, followed by a short hyperpolarization and a rebound of excitation. The rhythmic hyperpolarizations in STN neurons during SWDs likely originate from a subpopulation of pallidal neurons exhibiting rhythmic bursting temporally correlated with the EEG spikes. The repetitive discharges in STN neurons accompanying absence seizures might convey powerful excitation to basal ganglia output nuclei and, consequently, may participate in the control of thalamocortical SWDs.

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Section: Pathophysiologysupporting

confidence: 86%

Rhythmic Bursting in the Cortico-Subthalamo-Pallidal Network during Spontaneous Genetically Determined Spike and Wave Discharges

Paz¹,

Deniau²,

Charpier³

2005

J. Neurosci.

110

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“…The possibility that absence seizures are modulated by the GABAergic striatonigral pathway has emerged from pharmacological studies in GAERS, suggesting that an increase or a decrease in the activity of the striatum could reduce or amplify, respectively, the occurrence of SWDs (Depaulis et al, 1988(Depaulis et al, , 1989Danober et al, 1998;Deransart et al, 1998Deransart et al, , 2000Deransart et al, , 2001Deransart and Depaulis, 2002) (see Introduction). Changes in the output of SONs associated with the occurrence and the termination of the SWD could be part of endogenous mechanisms controlling the maintenance and the duration of the abnormal oscillations in the thalamocortical loops during absence seizures.…”

Section: Possible Implications For the Control Of Absence Seizuresmentioning

confidence: 99%

“…Recent pharmacological studies performed in genetic absence epilepsy rats from Strasbourg (GAERS), a well established genetic model of absence epilepsy (Marescaux et al, 1992;Danober et al, 1998), indicate that the basal ganglia circuits could act as a remote control system for absence seizures via a modulation of activity in the striatonigral pathway (Depaulis et al, 1988(Depaulis et al, , 1989Danober et al, 1998;Deransart et al, 1998Deransart et al, , 2000Deransart et al, , 2001Deransart and Depaulis, 2002). Specifically, the frequency of absence seizures is significantly decreased by injection of GABA A receptor agonists into the substantia nigra pars reticulata (SNr) or by the activation of GABAergic striatonigral neurons after intrastriatal injection of NMDA or dopaminergic D 1 receptor agonists (Depaulis et al, 1988;Deransart et al, 1998).…”

Section: Introductionmentioning

confidence: 99%

“…Specifically, the frequency of absence seizures is significantly decreased by injection of GABA A receptor agonists into the substantia nigra pars reticulata (SNr) or by the activation of GABAergic striatonigral neurons after intrastriatal injection of NMDA or dopaminergic D 1 receptor agonists (Depaulis et al, 1988;Deransart et al, 1998). Conversely, the pharmacological blockade of GABA A receptors in the SNr or the blockade of striatal D 1 receptors aggravates absence seizures (Deransart et al, 2000(Deransart et al, , 2001. These findings suggest that an increase or a decrease in the activity of GABAergic striatal output neurons (SONs) would attenuate or amplify, respectively, the occurrence of abnormal thalamocortical oscillations.…”

Section: Introductionmentioning

confidence: 99%

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On the Activity of the Corticostriatal Networks during Spike-and-Wave Discharges in a Genetic Model of Absence Epilepsy

Slaght¹,

Paz²,

Chávez³

et al. 2004

J. Neurosci.

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Absence seizures are characterized by impairment of consciousness associated with widespread bilaterally synchronous spike-and-wave discharges (SWDs) in the electroencephalogram (EEG), which reflect highly synchronized oscillations in thalamocortical networks. Although recent pharmacological studies suggest that the basal ganglia could provide a remote control system for absence seizures, the mechanisms of propagation of epileptic discharges in these subcortical nuclei remain unknown. In the present study, we provide the first description of the electrical events in the corticostriatal pathway during spontaneous SWDs in the genetic absence epilepsy rats from Strasbourg (GAERS), a genetic model of absence epilepsy. In corticostriatal neurons, the SWDs were associated with suprathreshold rhythmic depolarizations in-phase with local EEG spikes. Consistent with this synchronized firing in their excitatory cortical afferents, striatal output neurons (SONs) exhibited, during SWDs, large-amplitude rhythmic synaptic depolarizations. However, SONs did not discharge during SWDs. Instead, the rhythmic synaptic excitation of SONs was shunted by a Cl Ϫ -dependent increase in membrane conductance that was temporally correlated with bursts of action potentials in striatal GABAergic interneurons. The reduced SON excitability accompanying absence seizures may participate in the control of SWDs by affecting the flow of cortical information within the basal ganglia circuits.

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“…The substantia nigra pars reticulata (SNR) has been implicated in the control of clonic seizures (20), whereas brainstem structures may be involved in the control of tonic seizures (21). The 130-Hz stimulation of the STN decreases the firing rate of SNR neurons and increases GABA levels in the SNR (16)(17)(18)(19)(20)(21)(22). Indeed, application of either muscimol or electrical stimulation directly in the anterior SNR is anticonvulsant, and the anterior SNR may mediate the anticonvulsant effects of STN manipulations (23,24).…”

Section: Figmentioning

confidence: 99%

The Effect of Electrical Stimulation of the Subthalamic Nucleus on Seizures Is Frequency Dependent

2003

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Summary:Purpose: Animal studies and anecdotal human case reports have indicated that the subthalamic nucleus (STN) may be a site of anticonvulsant action.Methods: We tested the hypothesis that continuous electrical stimulation of the STN inhibits seizures acutely. We determined the effects of three stimulation frequencies, 130 Hz, 260 Hz, and 800 Hz, on generalized clonic and tonic-clonic flurothyl seizures. Adult male rats were implanted with concentric bipolar stimulating electrodes in the STN bilaterally. After recovery, rats underwent flurothyl seizures to compare the effects of each stimulation frequency on seizure threshold. Rats were tested 4 times, twice in the stimulated condition, and twice in the unstimulated condition. The order of trials was random, except that stimulation trials alternated with control trials. Flurothyl seizure thresholds under each stimulation condition were compared with control values from the same animal.Results: Bilateral stimulation of the STN at 130 Hz produced a significant increase in the seizure threshold for clonic flurothyl seizures, whereas stimulation at 260 Hz did not appear to have any effect on seizures. STN stimulation at 800 Hz significantly lowered seizure threshold for tonic-clonic seizures.Conclusions: We conclude that electrical stimulation of the STN can be anticonvulsant, but the effects appear to depend on the stimulation frequency and the type of seizure.

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Inhibition of the substantia nigra suppresses absences and clonic seizures in audiogenic rats, but not tonic seizures: evidence for seizure specificity of the nigral control

Cited by 73 publications

References 41 publications

Rhythmic Bursting in the Cortico-Subthalamo-Pallidal Network during Spontaneous Genetically Determined Spike and Wave Discharges

Rhythmic Bursting in the Cortico-Subthalamo-Pallidal Network during Spontaneous Genetically Determined Spike and Wave Discharges

On the Activity of the Corticostriatal Networks during Spike-and-Wave Discharges in a Genetic Model of Absence Epilepsy

The Effect of Electrical Stimulation of the Subthalamic Nucleus on Seizures Is Frequency Dependent

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