Gonadotropin-releasing hormone modulates voltage-activated sodium current and odor responses in Necturus maculosus...

The terminal nerve (nervus terminalis) extends from the basal forebrain to the nasal cavity and has been shown to contain gonadotropin-releasing hormone (GnRH). The specific function of the terminal nerve is unknown, but it has been hypothesized that it modulates the function of olfactory neurons. To examine the effects of GnRH on isolated Necturus maculosus olfactory sensory neurons (OSNs), we used the perforated configuration of the patch clamp technique to record current responses. GnRH had no effect on the membrane current at any holding potential but did modulate voltage-activated TTX-sensitive sodium current (INa). Within 1 min of applying GnRH, approximately 60% of the OSNs showed a decrease in the magnitude of INa. Initial responses to GnRH were inhibitory, although in one group of cells the initial inhibitory response was followed by a potentiation of INa with continual application (approximately 5 min). The time course of the GnRH response suggested that a second messenger pathway mediated the response. Inhibitors of PKC, tyrosine kinase, and PI3K were all able to inhibit the INa, but none of them could prevent the GnRH response. Application of a cAMP analog mimicked the effects of GnRH, and only inhibitors of PKA and PKG could prevent GnRH-induced inhibition of INa. This suggests that the modulation of voltage-activated sodium currents by GnRH involve a cyclic nucleotide pathway. In addition, GnRH modulated the odor responses of OSNs. Our data suggest the release of GnRH, presumably from the terminal nerve, can serve to modulate olfactory sensory neurons.