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13. Epilepsy, human and experimental EFFECTS OF TRH ON HIPPOCAMPAL PYRAMIDAL CELLS OF SPONTANEOUSLY EPILEPTIC RATS, A DOUBLE MUTANT. MASASHI SASA~ HISAMITSU UjIHARA*, KUMATOSHI ISHIHARA*, JOJl NAKAMURA*~ AND SHUJI TAKAORI, Department of Pharmacology, Faculty of Medicinep Kyoto University, Sakyo-ku, Kyoto 606, Japan.

Thyrotropin-releasing hormone (TRH) is reportedly effective in treatment of severe child epilepsy. Thus, we examined the effects of TRH on absence-like seizures characterized by the appearance of 5-7 Hz spike-wave complexes in the EEG and tonic seizures in spontaneously epileptic rats (SER: zi_/z~i tin/tin) that were obtained by mating zitter rats (zi/zi) with heterozygous tremor rats (tin/+). TRH (I-I0 mg/kg, i.v.) inhibited both absence-like and tonic seizures. In hippocampal slice preparations, stimulation of the mossy fiber usually induced repetitive firing in CA3 pyramidal cells of SER aged 12-14 weeks {adult SER) when both seizures appeared, but induced only one spike in those of SER aged 6-7 weeks {young SER) before the appearance of epileptic seizures, as well as in littermates (zi/zi, +/-) and Kyo:Wistar rats {controls). TRH of 0.I-I mM inhibited the repetitive firing elicited by mossy fiber stimulation but did not affect the single spike in young SER and control rats nor repetitive

• 2 + ~ . . firing seen m Mg -free medium m control rats. Mossy fiber stimulation-induced repetitive firing in adult SER was also inhibited by noradrenaline and dopamine. The inhibition by TRH of the repetitive firing in SER was antagonized by baloperidol, but not by phentolamine. These results suggest that TRH releases dopamine from the nerve terminals, thereby inhibiting the repetitive firing of pyramidal cells involved in the epileptic seizures in adult SER.

LONG-TERM POTENTIATION (LTP) OF ENTORHINAL AND HIPPOCAMPAL RESPONSES BY AMYGDALA STIMULATION. SHIUSHI MATSUURA, Department of Physiology, Osaka City University Medical School, Abeno-ku, Osaka 545, Japan

Field potentials of entorhinal cortex and hippocampus to amygdala stimulation were simultaneously recorded with tungsten wire electrodes to study the changes in behavioral seizures and LTP in response to amygdala kindling stimulation by 0.5 msec rectangular pulses of 10 Hz with 10 sec train duration. The intensity was set to the afterdischarge (AD) threshold for amygdala EEG. Electrodes were implanted 2-3 days before kindling. The entorhinal LTP was especially strong in the first kindling stimulation and gradually increased with successive stimulations, with gradual progression of AD and the behavioral seizure stage as well. In the hippocampns, LTP was almost undiscernible for the first kindling stimulation without AD in the hippocampal EEG and later increased markedly, as opposed to entorhinal responses. The enhancement of entorhinal LTP in comparison to the control response occurred more easily in suckling rats (16-18 days of age) than in adult rats. with a progression in kindling seizure stages. LTP of the entorhinal and hippocampal responses in the kindled rats was enhanced for all intensities of test pulses and showed an upward shift of the input-output (I/0) relationship from the control I/0 curve to test stimuli(0.3Hz) only. The results suggest that potentiation at the first relay synapses from the stimulated site could result in a sequential progression of the mechanisms for synaptic potentiation in neurons along the multisynaptic pathway, eventually leading to generalized behavioral convulsions; and that easier enhancement of LTP in excitatory synaptic transmission by kindling stimulations in sucklings as opposed to adults may contribute to the earlier acquisition of kindling phenomena in suckling rats.

INHIBITORY EFFECT OF PHENYTOIN ON BURSTING ACTIVITY INDUCED BY INTRACELLULAR CALCIUM INCREASE IN PRIMARY CULTURED NEURONS FROM MOUSE CEREBRAL CORTEX. TAKAGI.T.,KAJIWARA.K.. TAKAGI.H.. YUYAMA.N. AND SUGAYA, E. Dept. Physiol.,Kanagawa Dental College. Yoknsuka. 238.Japan

To clarify the anticonvulsant mechanism of phenytoin ,we evaluated the effect of phenytein on bursting activity induced by various agents that increase intraeellular calcium concent- ration in primary cultured neurons from the cerebral cortex of the ddY mouse.

By examination using the whole-cell patch current clamp.application of agents that increase intracellular calcium induced membrane hyperpolarization followed by clear bursting activity. The voltage clamp measurement showed that bursting activity was triggered by periodic inward current caused by intracellular calcium increase. The reversal potential of this current was -1OmV. Phenytoin did not prevent bursting activity induced by extracellular application of dibutyryl cyclic AMP.caffeine or calcium ionophore A23187 and intracellular application of calcium or TEA. However.bursting activity induced by PTZ and intracellular IP3 application was completely abolished by extracellular phenytnin application.

These results indicate that phenytoin action was not due to changes after intracellular calcium increase.but due to inhibition of calcium release from intracellular calcium reservoirs.