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The Journal of Neuroscience, February 23, 2005, 25(8):2092-2101; doi:10.1523/JNEUROSCI.4689-04.2005

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

Jeanne Tamar Paz, Jean-Michel Deniau, and Stéphane Charpier

Institut National de la Santé et de la Recherche Médicale U114, Chaire de Neuropharmacologie, Collège de France and U667, 75231 Paris Cedex 05, France

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.

Key words: absence epilepsy; basal ganglia; burst firing; corticosubthalamic neurons; in vivo; subthalamic neurons

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Received Nov 16, 2004; revised January 7, 2005; accepted January 8, 2005.

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