Gonadotropin-inhibitory hormone (GnIH) was originally identified in the Japanese quail as a hypothalamic neuropeptide inhibitor of pituitary gonadotropin synthesis and release. GnIH neuronal fibers not only terminate in the median eminence to control anterior pituitary function but also extend widely in the brain, suggesting multiple roles in the regulation of behavior. To identify the role of GnIH neurons in the regulation of behavior, we tested the effect of RNA interference (RNAi) of the GnIH gene on aggressive and sexual behaviors of white-crowned sparrows and Japanese quail. Administration of small interfering RNA against GnIH precursor mRNA (GnIH siRNA) into the third ventricle of white-crowned sparrows reduced resting time, spontaneous production of complex vocalizations, and stimulated brief agonistic vocalizations. These behaviors resembled those of breeding birds during territorial defense. Central administration of GnIH siRNA induced aggressive and sexual behaviors and GnIH administration suppressed GnIH RNAi induced aggressive and sexual behaviors in the male quail. In summary, GnIH may function as a central nervous system suppressor of social interaction, thus playing an important role in the control of reproductive behavior, general aggression and territorial defense.
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