An ascending seizure-controlling pathway in the medial brainstem and thalamus.
This study demonstrated that an ascending pathway from the laterodorsal tegmental nucleus (LDTg) of the pontomesencephalic tegmentum to the thalamic central medial intralaminar nucleus (CeM) controls the thresholds of experimental seizures. Electrolytic and excitotoxic lesions of the CeM and adjacent thalamus facilitated myoclonic, facial-forelimb clonic, and tonic pentylenetetrazol seizures. Microinjections of the GABAB agonist (-)baclofen in the LDTg facilitated myoclonic and facial-forelimb clonic but not tonic seizures. When LDTg injections of (-)baclofen were performed in animals with prior electrolytic lesions of the midline thalamus, the thresholds of myoclonic and facial-forelimb clonic seizures were unchanged compared to similarly lesioned rats with control vehicle LDTg injections. In addition, the lowering of tonic seizure threshold observed with thalamic lesions was reversed by these (-)baclofen injections. Taken together with past studies, these results imply that the LDTg controls myoclonic and facial-forelimb clonic seizures via ascending projections to the CeM and possibly other medial thalamic nuclei. We also postulate that the LDTg affects tonic seizures by two different, opposing pathways. Although the LDTg-CeM pathway is part of the "ascending reticular activating system," lesions of the midline thalamus did not affect spontaneous sleep, implying that the CeM does not have an essential role in sleep regulation.
Department of Neurology, Washington University School of Medicine, St. Louis, Missouri 63110.
J W
JW
Miller
B C
BC
Gray
G M
GM
Turner
M E
ME
Bardgett
D000818:Animals; D001143:Arousal; D001418:Baclofen / Q000494:pharmacology; D001927:Brain Diseases / Q000503:physiopathology; D005260:Female; D009434:Neural Pathways / Q000503:physiopathology; D051381:Rats; D012640:Seizures / Q000503:physiopathology*; D012890:Sleep; D013681:Tegmentum Mesencephali / Q000503:physiopathology*; D013786:Thalamic Diseases / Q000139:chemically induced / Q000503:physiopathology*; D013788:Thalamus / Q000503:physiopathology*
D001418:Baclofen