Thyrotropin-releasing hormone has profound presynaptic action on cultured spinal cord neurons

Thyrotropin-releasing hormone (TRH) receptors are widely distributed throughout the nervous system. In particular, both the dorsal and the ventral horn (VH) neurons contain a rich distribution of TRH receptors, and TRH application to these sites has profound physiological effects. Currently the mechanism of action of TRH is not known. We examined the effect of TRH on ventral horn neurons using intracellular and patch-clamp techniques. Our results indicate that TRH application profoundly increases the firing rate of VH cells by decreasing membrane conductance. More importantly, TRH causes a significant increase in frequency and amplitude of postsynaptic potentials. Under voltage-clamp condition, TRH reduces holding current and causes a significant increase in the rate of occurrence and the amplitude of excitatory postsynaptic currents (EPSCs), an effect that lasts for more than 5 minutes. This effect of TRH is not observed in cultured neurons pretreated with tetanus toxin. TRH also fails to alter the characteristics of the EPSCs when it is applied to a region of the cell that is sparsely innervated. These results provide strong evidence that presynaptic mechanisms have a significant role in the excitatory effect of TRH on the VH neurons. Because there is evidence that trophic factors are released from presynaptic terminals, by increasing synaptic activity, TRH can have a trophic influence on the spinal cord neurons. In addition, because there are a significant number of TRH containing neurons within the spinal cord, it is likely that TRH has a major role in information processing within the spinal cord.