An Electrophysiological Study of the Effects of Thyrotropin Releasing Hormone (TRH) on Ca1 Pyramidal Neurons of the Rat Hippocampal Slice Preparation

The electrophysiological action of TRH, a neuropeptide largely present in the CNS, was studied in a thick slice preparation of the rat hippocampus with intracellular techniques. Bath applications of TRH (5-20μM) did not affect either the input resistance or the resting potential of pyramidal cells (n=76). When a train of spikes elicited activation of Ca2+dependent K+ conductances resulting into an afterhyperpolarization (AHP), the AHP was decreased in amplitude by TRH which left unchanged the number of spikes and the interspike intervals. A voltage clamp study of high threshold voltage activated Ca2+ (HV A) conductances showed no effect of the neuropeptide on these currents measured at steady state. Excitatory postsynaptic potentials (EPSPs), mediated both by NMDA and AMPA receptors, evoked after extracellular stimulation of the Schaffer collateral fibers were pharmacologically isolated. In TRH a transient and cospicuous potentiation of NMDA receptor mediated EPSPs was observed. The effect was specific since it did not affect AMPA receptor mediated responses. Bath application of NMDA (lOμM) or AMPA (5μM) was tested on the same neurons. Unlike AMPA-induced responses, responses evoked by bath-applied NMDA were also transiently enhanced. A similar specific modulation was shown when the same protocol was applied in the presence of 1μM TTX, which suggests a very likely postsynaptic site of action of TRH. GABA mediated inhibitory postsynaptic potentials were evoked after stimulation of different regions of the hippocampus ( i.e. stratum lacunosum mo/ecu/are, LM and stratum pyramida/e, SP). TRH was decreasing the peak amplitude of GABAA receptor mediated responses regardless of the site of stimulation. On the other hand, GABAB receptor mediated responses were diminished only when evoked from the SP. Bath applications of isoguvacine and baclofen (10μM), GABAA and GABAB agonists respectively, elicited responses unaffected by TRH. These findings suggest a site of action of TRH which involves the presynaptic circuit. Fmally, long and short term potentiation (STP/L TP) was induced in control condition (IOμM picrotoxin) and after TRH delivery. TRH blocked the induction of the potentiation. In conclusion, TRH enhanced the excitability of pyramidal neurons by a combination of enhancement of excitatory transmission and depression of inhibitory one. In case of strong stimulation (i.e. STP/L TP) it tends to occlude further potentiation, suggesting its role of "dampern in the hippocampus