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The Journal of Neuroscience, January 24, 2007, 27(4):929-941; doi:10.1523/JNEUROSCI.4677-06.2007

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Neurobiology of Disease
Activity of Ventral Medial Thalamic Neurons during Absence Seizures and Modulation of Cortical Paroxysms by the Nigrothalamic Pathway

Jeanne Tamar Paz,^1,2 Mario Chavez,³ Sandrine Saillet,^1,2,4 Jean-Michel Deniau,^1,2 and Stéphane Charpier^1,2

¹Institut National de la Santé et de la Recherche Médicale (INSERM), Unité 667, Collège de France, F-75231 Paris, France, ²Université Pierre et Marie Curie, F-75005 Paris, France, ³Centre National de la Recherche Scientifique Unité Propre de Recherche 640, Laboratoire de Neurosciences Cognitives et Imagerie Cérébrale, Hôpital de la Pitié Salpêtrière, and ⁴INSERM, Unité 739, Hôpital de la Pitié Salpêtrière, F-75651 Paris, France

Correspondence should be addressed to Jeanne Tamar Paz, Institut National de la Santé et de la Recherche Médicale, Unité 667, Collège de France, F-75231 Paris, France. Email: jeanne.paz{at}college-de-france.fr

Absence seizures are characterized by bilaterally synchronous spike-and-wave discharges (SWDs) in the electroencephalogram, which reflect abnormal oscillations in corticothalamic networks. Although it was suggested that basal ganglia could modulate, via their feedback circuits to the cerebral cortex, the occurrence of SWDs, the cellular and network mechanisms underlying such a subcortical control of absence seizures remain unknown. The GABAergic projections from substantia nigra pars reticulata (SNR) to thalamocortical neurons of the ventral medial (VM) thalamic nucleus provide a potent network for the control of absence seizures by basal ganglia. The present in vivo study provides the first description of the activity of VM thalamic neurons during seizures in the genetic absence epilepsy rats from Strasbourg, a well established model of absence epilepsy. Cortical paroxysms were accompanied in VM thalamic neurons by rhythmic bursts of action potentials. Pharmacological blockade of excitatory inputs of nigrothalamic neurons led to a transient interruption of SWDs, correlated with a change in the activity of thalamic cells, which was increased in frequency and converted into a sustained arrhythmic firing pattern. Simultaneously, cortical neurons exhibited a decrease in their firing rate that was associated with an increase in membrane polarization and a decrease in input resistance. These new findings demonstrate that an inhibition of SNR neurons changes the activity of their thalamic targets, which in turn could affect cortical neurons excitability and, consequently, the generation of cortical epileptic discharges. Thus, the nigro-thalamo-cortical pathway may provide an on-line system control of absence seizures.

Key words: ventral medial thalamic nucleus; absence epilepsy; basal ganglia; in vivo; substantia nigra pars reticulate; GAERS

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Received Oct. 27, 2006; revised Nov. 28, 2006; accepted Dec. 17, 2006.

Correspondence should be addressed to Jeanne Tamar Paz, Institut National de la Santé et de la Recherche Médicale, Unité 667, Collège de France, F-75231 Paris, France. Email: jeanne.paz{at}college-de-france.fr

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