title: Involvement of the thalamic parafascicular nucleus in mesial temporal lobe epilepsy.
abstract: Mesial temporal lobe epilepsy (MTLE) is characterized by focal seizures, associated with hippocampal sclerosis, and often resistance to antiepileptic drugs. The parafascicular nucleus (PF) of the thalamus is involved in the generation of physiological oscillatory rhythms. It receives excitatory inputs from the cortex and inhibitory inputs from the basal ganglia, a system implicated in the control of epileptic seizures. The aim of this study was to examine the involvement of the PF in the occurrence of hippocampal paroxysmal discharges (HPDs) in a chronic animal model of MTLE in male mice. We recorded the local field potential (LFP) and the extracellular and intracellular activity of hippocampal and PF neurons during spontaneous HPDs in vivo. The end of the HPDs was concomitant with a slow repolarization in hippocampal neurons leading to an electrical silence. In contrast, it was associated in the PF with a transient increase in the power of the 10-20 Hz band in LFPs and a depolarization of PF neurons resulting in a sustained firing. We tested the role of the PF in the control of HPDs by single 130 Hz electrical stimulation of this nucleus and bilateral intra-PF injection of NMDA and GABA(A) antagonist and agonist. High-frequency PF stimulation interrupted ongoing HPDs at an intensity devoid of behavioral effects. NMDA antagonist and GABA(A) agonist suppressed hippocampal discharges in a dose-dependent way, whereas NMDA agonist and GABA(A) antagonist increased HPDs. Altogether, these data suggest that the PF nucleus plays a role in the modulation of MTLE seizures.
authors.affiliation: Grenoble Institut des Neurosciences, Institut National de la Santé et de la Recherche Médicale U 836-Université Joseph Fourier-Commisariat à l'Energie Atomique Centre Hospitalier Universitaire, 38700 La Tronche, France.
authors.forename: Mélanie
authors.initials: M
authors.lastname: Langlois
authors.forename: Pierre-Olivier
authors.initials: PO
authors.lastname: Polack
authors.forename: Hélène
authors.initials: H
authors.lastname: Bernard
authors.forename: Olivier
authors.initials: O
authors.lastname: David
authors.forename: Stéphane
authors.initials: S
authors.lastname: Charpier
authors.forename: Antoine
authors.initials: A
authors.lastname: Depaulis
authors.forename: Colin
authors.initials: C
authors.lastname: Deransart
mesh_terms: D015763:2-Amino-5-phosphonovalerate / Q000031:analogs & derivatives / Q000494:pharmacology; D000200:Action Potentials / Q000187:drug effects / Q000502:physiology; D000818:Animals; D055592:Biophysical Phenomena / Q000187:drug effects / Q000502:physiology; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D004569:Electroencephalography / Q000379:methods; D004833:Epilepsy, Temporal Lobe / Q000139:chemically induced / Q000188:drug therapy / Q000473:pathology*; D005073:Evoked Potentials, Somatosensory / Q000187:drug effects / Q000502:physiology; D018691:Excitatory Amino Acid Antagonists / Q000494:pharmacology; D007839:Functional Laterality / Q000187:drug effects / Q000502:physiology; D058785:GABA-A Receptor Agonists / Q000494:pharmacology; D006624:Hippocampus / Q000187:drug effects / Q000473:pathology / Q000502:physiology; D020646:Intralaminar Thalamic Nuclei / Q000187:drug effects / Q000473:pathology* / Q000503:physiopathology; D007608:Kainic Acid; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D009118:Muscimol / Q000494:pharmacology; D016202:N-Methylaspartate / Q000494:pharmacology; D009474:Neurons / Q000502:physiology; D018709:Statistics, Nonparametric; D013997:Time Factors; D014851:Wakefulness
chemical_list: D018691:Excitatory Amino Acid Antagonists; D058785:GABA-A Receptor Agonists; C064539:2-amino-4-methyl-5-phosphono-3-pentenoic acid; D009118:Muscimol; D016202:N-Methylaspartate; D015763:2-Amino-5-phosphonovalerate; D007608:Kainic Acid