Abstracts

It has been reported that the most of the neurons in reticular thalamus (RT) are GABAergic, and there are fiber connections from RT to other thalamic nuclei through which their functions are modulated. According to the previous studies, it is assumed that the GABAergic system inhibits kainic acid (KA)-induced mesencephalic reticular formation (MRF) seizures. To ellucidate the role of RT in generalized seizures, we investigated the effect of muscimol injection into RT during generalized status epilepticus induced by a KA microinjection into unilateral MRF in rats. A microinjection of KA into unilateral MRF resulted in recurrent generalized seizures in unrestrained rats (Tanaka et al., 1994).
Twenty male Wistar rats underwent stereotactic implantation of electrodes in the left RT (LRT), the left MRF (LMRF), the bilateral dorsal hippocampus (LdH, RdH), and the bilateral sensorimotor cortex (LCx, RCx). For KA injection, stainless steel cannula was inserted into LMRF and LRT. After recovery from surgery, all rats received KA (2.0 microg) injection into LMRF. Five hours after KA injection, while rats were exhibiting generalized status epilepticus, muscimol (100mM, 1 microg, n=10) were injected into LRT.
In the controls, the rats received the same amount of PBS (phosphate-buffered saline solution , n=10). Electrophysiologic and behavioral observation was made.
Initially, periodic synchronous spike discharges were observed in all recorded sites 2 hours after KA injection. The rats showed only immobilization. Three to five hours after KA injection, multiple synchronous spike discharges appeared on EEG. In this time, the rats showed generalized tonic convulsion followed by short clonic seizures. One hour after muscimol injection, overall seizures aggravated on EEG. Behaviorally, motor manifestations continued, and 40% of the rats died within 24 hours. One hour after PBS injection, further electrophysiologic and behavioral change were not seen.
(1) Generalized status epilepticus was induced by a KA injection into LMRF.
(2) In the rats received muscimol into LRT, periodic multiple synchronous spike discharges were severer than that of the controls on EEG.
Behaviorally, crucial seizures continued, and 40% of the rats died within 24 hours.
(3) Unlike prior studies, our results suggested that muscimol injection into the RT inhibited function of GABAergic neurons of RT, which markedly aggravated MRF seizures.
[Supported by: Grant-in-Aid for Priority Areas Research (C) from the Ministry of Education, Sciences, and Culture of Japan]