Journal of Neuroscience, Vol 4, 2410-2417, Copyright © 1984 by Society for Neuroscience
Evidence implicating substantia nigra in regulation of kindled seizure threshold
JO McNamara, MT Galloway, LC Rigsbee and C Shin
We 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 colonic 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 substantia nigra (SN) markedly suppressed both motor and
limbic seizures induced by stimulation of amygdala, olfactory structures,
or lateral entorhinal cortex. Microinjection of saline did not suppress
seizures. The suppressive effect of muscimol: (i) dissipated after several
hours and was dependent on dose; (ii) was due to an elevation of the
seizure threshold, since typical seizures could be elicited with electrical
current far exceeding the threshold; and (iii) exhibited spatial
specificity since muscimol injections 1 to 2 mm dorsal to the SN or into
neocortex did not suppress the seizures. The actions of muscimol were
probably mediated by its GABA agonist properties, since microinjection of
an irreversible inhibitor of GABA transaminase (gamma- vinyl GABA) into the
area of the SN also suppressed kindled seizures. Destruction of brainstem
structures was produced by microinjection of the neurotoxin,
N-methyl-D,L-aspartate. Seizures were markedly suppressed in animals with
bilateral destruction of the SN but not in animals in which the SN was
spared bilaterally. We interpret the data to 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.
