EN
Gonadotropin releasing hormone (GnRH) neurons control fertility centrally. The neuromodulator kisspeptin (kiss) strongly activates GnRH neurons via its G-protein coupled receptor 54 (GPR54). GnRH neurons express GPR54, implicating direct actions of kiss on these cells; however, GPR54 is broadly expressed in the brain, suggesting indirect actions are possible. Estradiol potentiates the GnRH neuron response to kiss, which recent work showed was due to kiss enhancement of excitatory GABA and glutamate transmission to GnRH neurons. Here we tested if the effect of kiss on GABA transmission to GnRH neurons is due to pre or postsynaptic mechanisms. We performed whole-cell voltage-clamp recordings of GABA miniature postsynaptic currents (mPSC) in GnRH neurons in the presence of tetrodotoxin (TTX), which minimizes presynaptic actions by blocking action potentials. Kiss had no effect on the frequency of GABA mPSCs, but did signifi cantly increase the amplitude of these events. To see if the effect of kiss on GABA PSC amplitude is mediated postsynaptically, we recorded currents generated by local GABA application. Kiss signifi cantly increased GABA-induced current amplitude. These data indicate that the kiss effect on frequency of GABA transmission to GnRH neurons is due to presynaptic actions, but effects on amplitude are postsynaptic. Together with previous fi ndings, these data provide additional insights into the mechanisms of direct and transsynaptic effects of kiss on GnRH neuronal activity.