PROLACTIN-RELEASING PEPTIDE ENHANCES SYNAPTIC TRANSMISSION IN RAT THALAMUS

摘要

Prolactin-releasing peptide (PrRP) is an RF-amide peptide that is believed to be the physiological ligand for the G-protein coupled receptor GPR10. This receptor is highly expressed in the GABAergic principal neurons of the reticular thalamic nucleus (RTN), but the cellular and physiological effects of receptor activation on thalamic function are not yet clear. The present study examined the effects of PrRP on excitatory and inhibitory synaptic transmission in the RTN and the ventrobasal complex (VB) of the thalamus. In RTN neurons, PrRP enhanced excitatory synaptic transmission by selectively increasing the amplitude of the NMDA receptor-mediated excitatory postsynaptic current (EPSC; NMDA-EPSC). AMPA receptor mediated current were not affected. A mutated form of PrRP with negligible affinity to GPR10 was ineffective, and no enhancement of NMDA-EPSCs was observed in the ventrobasal thalamus, which does not express GPR10. The effect was distinct from that of neuropeptide FF (NPFF), which enhanced both AMPA and NMDA receptor mediated responses and probably acted though a presynaptic NPFF receptor. Taken together, these results suggest that PrRP selectively modulates NMDA receptor-mediated synaptic transmission in RTN neurons through postsynaptic GPR10 receptors. This effect appears to involve an unconventional mechanism because it was not blocked by intracellularly applied GDPbetaS. PrRP also increased by 50-75% the amplitude of GABA_A receptor-mediated inhibitory postsynaptic current (IPSCs) in both ventrobasal nucleus and RTN neurons. The former represents inhibitory input from RTN neurons to thalamocortical relay cells and the latter a local inhibition produced by RTN axon collaterals. Miniature IPSC analysis revealed that PrRP enhanced release of GABA and thus acted presynaptically. In conclusion, PrRP increases both excitatory and inhibitory synaptic transmission in the thalamus via distinct mechanisms, and the receptors responsible for these actions are in all cases present in the principal neuron of the RTN.