Contribution of intralaminar thalamic nuclei to spike-and-wave-discharges during spontaneous seizures in a genetic rat model of absence epilepsy.
In an epileptic rat model of generalized absence epilepsies, the genetic absence epilepsy rats from Strasbourg (GAERS), simultaneous recordings of bilateral epidural electroencephalogram (EEG) of the prefrontal cortex and unit activity of neurons in the intralaminar centrolateral (CL) and paracentral thalamic nucleus (PC) were performed under neurolept-anaesthesia (fentanyl-dehydrobenzperidol analgesia). Spike-and-wave (SW) seizures in these rats are characterized by generalized 7-10 Hz spike-and-wave discharges (SWDs) on the EEG. All neurons recorded in intralaminar thalamic nuclei during spontaneous SWDs showed high-frequency (average 368 Hz, range 200-500 Hz), burst-like activity, which occurred in a highly synchronized fashion with every SWD or with alternating SWD-complexes. Burst discharges in intralaminar neurons were delayed by 13.1 ms (CL) and 12.7 ms (PC), with respect to the spike component of a given SWD on the EEG, whereas burst discharges in the ventrobasal thalamus (VB) and in the rostral nucleus reticularis thalami (rRT) preceded the spike component by 17.8 ms and 8.3 ms, respectively. The onset of SWDs on the EEG was preceded by a tonic firing pattern (20-50 Hz) in about one third of CL and PC neurons. Microiontophoretic application of the gamma-aminobutyric acid (GABA)A receptor antagonist bicuculline aggravated, whereas, the glutamate receptor antagonists DNQX and APV dampened, SWD-related discharges in PC and CL; the GABAB receptor antagonist CGP 35347 had no measurable effect. These data indicate that intrathalamic nuclei are recruited rhythmically during SWDs, through mechanisms that seem to rely on a delayed glutamatergic excitation modulated by GABAergic influences, rather than a GABA-mediated rebound burst activity typical of relay cells. The finding of a temporal delay of SWD-related activity in intrathalamic, compared with "specific" thalamic relay nuclei, does not support the notion of a leading or pacemaker role in SWD generation. It is, however, rather suggestive of a function of intrathalamic neurons during synchronization and maintenance of neuronal oscillations, and these intrathalamic neurons may be recruited through glutamatergic corticofugal inputs.
Seidenbecher
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Otto-von-Guericke Universität, Medizinische Fakultät, Institut für Physiologie, Leipziger Str. 44, D-39120 Magdeburg, Germany.
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D000200:Action Potentials; D000818:Animals; D001640:Bicuculline / Q000494:pharmacology; D004569:Electroencephalography; D004594:Electrophysiology; D004832:Epilepsy, Absence / Q000235:genetics* / Q000503:physiopathology*; D018756:GABA Antagonists / Q000494:pharmacology; D058787:GABA-A Receptor Antagonists; D058788:GABA-B Receptor Antagonists; D020646:Intralaminar Thalamic Nuclei / Q000503:physiopathology*; D008297:Male; D009474:Neurons / Q000502:physiology; D051381:Rats; D011922:Rats, Mutant Strains; D011930:Reaction Time; D011999:Recruitment, Neurophysiological; D012640:Seizures / Q000503:physiopathology*
D018756:GABA Antagonists; D058787:GABA-A Receptor Antagonists; D058788:GABA-B Receptor Antagonists; D001640:Bicuculline