Mechanisms of neuromodulation by a nonhypophysiotropic GnRH system controlling motivation of reproductive behavior in the teleost brain

Fine tuning of the nervous system in response to intrinsic and extrinsic cues is necessary for successful reproductive behavior. Gonadotropin releasing hormone (GnRH) was originally identified as a hypophysiotropic hormone that facilitates the release of gonadotropins from the pituitary. Although later studies reported their presence, the nonhypophysiotropic GnRH systems, which consist of two groups located in the terminal nerve (TN) and the midbrain tegmentum, respectively, has long been overshadowed by the hypophysiotropic GnRH system. By taking advantage of the teleost brains in which all three GnRH systems are well developed, the anatomical and electrophysiological properties of all three groups of GnRH neurons have been studied. However, despite our increasing endocrinological knowledge, we know very little about the manner of information flow by nonhypophysiotropic neuromodulatory GnRH neurons in the brain. In this article, we will review recent advances in the studies of nonhypophysiotropic GnRH neurons from cellular to behavioral levels. We will first discuss general features of the information processing by peptides and then introduce our recent approaches toward the understanding of the excitation-secretion coupling mechanism of single GnRH neuron using our newly developed primary culture system of isolated TN-GnRH3 neurons. We also introduce autocrine/paracrine regulation of TN-GnRH3 neurons by NPFF peptides for synchronization among them. In addition, we highlight recent advances in the neuromodulatory action of GnRH peptide on the information processing of sensory neuronal circuits and reproductive behavior. These multidisciplinary approaches will greatly advance our understanding of the complex action of GnRH peptides in relation to the brain control of reproduction.