Effects of thyrotropin-releasing hormone on evoked responses and long-term potentiation in dentate gyrus of rat.

Thyrotropin-releasing hormone (TRH), a neuropeptide with multiple neuromodulatory functions, has been receiving examination for clinical relevance in epilepsy. To investigate the neurophysiologic properties of the anticonvulsant action of TRH, its effects on the evoked responses and long-term potentiation (LTP) of the perforant path input to the dentate gyrus were examined in anesthetized rats. Intracerebroventricular microinjected 80 micrograms TRH increased the relationship between the amplitude of the population spike and the slope of the EPSP, and reduced the LTP of the EPSP by approximately 30% compared with saline-injected controls. The TRH, however, slightly increased the amplitude of the population spike. These effects of TRH on LTP were confirmed in a dose-related manner. These results indicate that TRH may have two independent effects in the dentate gyrus, an increase in cellular excitability and a decrease in synaptic plasticity. The latter may be related to the previously reported anticonvulsant effects on kindling.