The neuropeptide thyrotropin-releasing hormone modulates GABAergic synaptic transmission on pyramidal neurones of the rat hippocampal slice.

The modulatory action of thyrotropin-releasing hormone (TRH), an endogenously occurring neuropeptide, on synaptic potentials mediated by activation of GABAA or GABAB receptors was studied using intracellular recordings from CA1 pyramidal neurones of the rat hippocampal brain slice preparation. Bath-applied TRH (10 microM) produced a reversible depression of fast IPSPs (mediated by GABAA receptors) induced by electrical stimulation of the stratum lacunosum moleculare (LM) or stratum pyramidale (SP). This phenomenon was not associated with changes in the IPSP reversal potential, resting potential, or input resistance. GABAB receptor-mediated slow IPSPs elicited by SP stimulation were found insensitive to TRH whereas those induced by LM stimulation were attenuated by the peptide. AMPA receptor-mediated EPSPs and postsynaptic responses to isoguvacine or baclofen were unchanged by TRH. These data suggest that the action of TRH on GABAergic transmission was probably exerted at presynaptic level within the local circuitry comprising CA1 neurones. Such an effect of TRH represents an interesting example of transient downregulation of inhibitory processes by a physiological neuropeptide and is expected to augment excitability of pyramidal cells.