Abstract
Sexual behavior is essential for the perpetuation of a species. In female rodents,
mate preference and lordosis behavior depend heavily on the integration of olfactory
cues into the neuroendocrine brain, yet its underlying neural circuits are not well
understood. We previously revealed that kisspeptin neurons in the anteroventral periventricular
nucleus/periventricular nucleus continuum (AVPv/PeN) are activated by male olfactory
cues in female mice. Here, we further reveal that male-directed mate preferences and
lordosis are impaired in kisspeptin knockout mice but are rescued by a single injection
with kisspeptin. Acute ablation of AVPV/PeN kisspeptin neurons in adult females impaired
mate preference and lordosis behavior. Conversely, optogenetic activation of these
neurons triggered lordosis behavior. Kisspeptin neurons act through classical GPR54/GnRH
signaling in stimulating mate preferences, but unexpectedly, GPR54/GnRH neuronal ablation
did not affect lordosis behavior. Therefore, to identify the downstream components
of the neural circuit involved in lordosis behavior, we employed genetic transsynaptic
tracing in combination with viral tract tracing from AVPV/PeN kisspeptin neurons.
We observed that kisspeptin neurons are communicating with neurons expressing the
neuronal form of nitric oxide synthase. These results suggest that hypothalamic nitric
oxide signaling is an important mechanism downstream of kisspeptin neurons in the
neural circuit governing lordosis behavior in female mice.
Keywords
sexual behavior - hypothalamus - olfaction - GnRH - nitric oxide