Electrical Stimulation of the Mammillary Nuclei Increases Seizure Threshold to Pentylenetetrazol in Rats


  • Marek A. Mirski,

    Corresponding author
    1. Department of Anesthesiology and Critical Care Medicine, Division of euroanesthesiology, Johns Hopkins University Hospital, Baltimore, Maryland
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  • Robert S. Fisher

    1. Epilepsy Center, Barrow Neurological Institute, St. Joseph's Hospital and Medical Center, Phoenix, Arizona, U.S.A.
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Address correspondence and reprint requests to Dr. M. A. Mirski at Department of Anethesiology and Critical Care Medicine, Division of Neuroanesthesiology, Johns Hopkins University Hospital, Meyer 8-134, 600 N. Wolfe St., Baltimore, MD 21205, U.S.A.


Summary: High-frequency electrical stimulation of mammillary nuclei (MN) of rat posterior hypothalamus resulted in a significant increase in seizure threshold induced by pentylenetetrazol (PTZ). The anticonvulsant effect was frequency and intensity specific. Stimulation at 100 Hz (1–5V, 30–200 μA) afforded protection against EEG and behavioral manifestations of PTZ seizures. Stimulation of either low frequency (5 Hz), high intensities (8–20 V, 300–800 μA), or outside the histologically verified MN target region did not increase seizure threshold. In some instances, high-intensity stimulation of MN alone elicited spike-wave epileptiform EEG activity accompanied by either arrest of behavior or myoclonic seizures. In animals with ongoing seizure activity, electrical stimulation of MN disrupted the high-voltage synchronous wave forms on cortical EEG. These data support the concept that electrical perturbation of MN in hypothalamus may functionally inhibit generalization of paroxysmal activity required for expression of the EEG and, in particular, the behavioral component of PTZ seizures. These studies provide additional insight into forebrain-brainstem interactions mediating generalized seizure expression.