Evidence implicating subtantia nigra in regulation of kindled seizure threshold

The authors studied the effects of microinjected drugs and brainstem lesions on motor and limbic seizures in the kindling model of epilepsy. The duration of motor seizures was determined by timing the clonic and tonic movements of the extremities. The duration of limbic seizures was determined by measuring afterdischarge recorded on the electroencephalogram. Bilateral microinjection of a gamma -aminobutyric acid (GABA) agonist, muscimol, into the area of the subtantia nigra (SN) markedly suppressed both motor and limbic seizues induced by stimulation of amygdala, olfactory structures, or lateral entorhinal cortex. The suppressive effect of muscimol: dissipated after several hours and was dependent on dose; was due to an elevation of the seizure threshold; exhibited spatial specificity since muscimol injection 1 to 2 mm dorsal to the SN or into neocortex did not suppress the seizures. The data indicate that the SN is the site at which the GABA agonists and lesions act to raise the threshold for kindled seizures. The suppression of limbic seizures indicates that this brainstem nucleus can regulate the intrinsic neuronal excitability of hemispheric sites.