Thyrotropin-releasing hormone enhances excitatory postsynaptic potentials in neocortical neurons of the rat in vitro.
Several lines of evidence suggest a modulatory effect of thyrotropin-releasing hormone (TRH) on synaptic transmission in the mammalian neocortex. In the present study, the effects of this tripeptide on intracellularly recorded neocortical pyramidal neurons were investigated using rat in vitro brain slice preparations. TRH (5 microM and 50 microM) added to the perfusion medium concentration-dependently increased the excitability of pyramidal neurons, reflected by the number of spikes evoked by a depolarizing current pulse and by the augmentation of the time integral of glutamatergic excitatory postsynaptic potentials (EPSPs). TRH increased preferentially the time integrals of the late components of EPSPs (1-EPSPs) and increased their voltage-dependence. The early components of the EPSPs (e-EPSPs) were changed to much lesser extent. Iontophoretically applied D-2-amino-5-phosphonovalerate (D-APV) antagonized the TRH-induced increase of the 1-EPSPs. TRH also markedly enhanced the depolarizing responses evoked by iontophoretically applied N-methyl-D-aspartate (NMDA), while the depolarizing responses evoked by (R,S)-alpha-amino-3-hydroxy-5-methyl-4-isoxazole-propionic acid (AMPA) and L-glutamate were not significantly affected. The depolarizing inward rectification present in all neurons studied was augmented by the higher concentration of TRH. The effects of TRH were incited after about 5 min and were long-lasting. In most neurons the effects of TRH on neuronal excitability did not completely recover during the 45 min washout period. The present data suggest that some of the non-hormonal actions of TRH in the neocortex may be due to an enhancement of glutamatergic synaptic transmission.(ABSTRACT TRUNCATED AT 250 WORDS)
Kasparov
S
S
Moscow Sechenov Medical Academy, Dept. of Pharmacology, Russia.
Pawelzik
H
H
Zieglgänsberger
W
W
D015763:2-Amino-5-phosphonovalerate / Q000494:pharmacology; D000818:Animals; D002540:Cerebral Cortex / Q000166:cytology / Q000187:drug effects* / Q000502:physiology; D004558:Electric Stimulation; D018698:Glutamic Acid / Q000494:pharmacology; D066298:In Vitro Techniques; D008297:Male; D008564:Membrane Potentials / Q000187:drug effects; D016202:N-Methylaspartate / Q000494:pharmacology; D009474:Neurons / Q000502:physiology*; D017966:Pyramidal Cells / Q000187:drug effects; D051381:Rats; D017207:Rats, Sprague-Dawley; D013569:Synapses / Q000187:drug effects* / Q000502:physiology; D009435:Synaptic Transmission / Q000187:drug effects*; D013973:Thyrotropin-Releasing Hormone / Q000037:antagonists & inhibitors / Q000494:pharmacology*; D018350:alpha-Amino-3-hydroxy-5-methyl-4-isoxazolepropionic Acid / Q000494:pharmacology
D018698:Glutamic Acid; D013973:Thyrotropin-Releasing Hormone; D016202:N-Methylaspartate; D015763:2-Amino-5-phosphonovalerate; D018350:alpha-Amino-3-hydroxy-5-methyl-4-isoxazolepropionic Acid