Modulation by TRH of NMDA-elicited responses of CA1 neurones of the rat hippocampal slice preparation.

Intracellular recording from CA1 neurones of the rat hippocampal slice preparation was carried out to assess the ability of the endogenously-occurring neuropeptide thyrotropin-releasing hormone (TRH) to modulate responses elicited by the excitatory amino acid agonist N-methyl-D-aspartate (NMDA). TRH (5 microM) produced no change in resting membrane potential or input resistance but facilitated on-going synaptic activity. In the continuous presence of the peptide responses to NMDA were selectively enhanced for about 20 min. In approximately 50% of cells the potentiating effect of TRH persisted in tetrodotoxin (TTX) solution and was associated with removal of the apparent voltage-dependent increase in input resistance usually found during the NMDA-induced depolarization. It is suggested that TRH evoked a transient upregulation of NMDA responses which might account for the reported facilitation by this peptide of long term potentiation in the hippocampus.