A comprehensive chemotyping and gonadal regulation of seven kisspeptinergic neuronal populations in the mouse brain

Background Kisspeptinergic signaling is well-established as crucial for regulation of reproduction, but its potential broader role in brain function is less understood. This study investigates the distribution and chemotyping of kisspeptin-expressing neurons within the mouse brain. Methods RNAscope singleplex, duplex and multiplex in situ hybridization methods were used to assess kisspeptin mRNA ( Kiss1) expression and its co-expression with other neuropeptides, excitatory and inhibitory neurotransmitter markers, and sex steroid receptors in intact and gonadectomized young adult mice. Results Seven distinct kisspeptin neuronal chemotypes were characterized, including within two novel Kiss1 -expressing groups described here for the first time: the ventral premammillary nucleus, and the nucleus of the solitary tract. Kiss1 mRNA was also localized in the soma, and within the dendritic compartment, of hypothalamic neurons. Altered Kiss1 expression following gonadectomy suggests a previously unappreciated role for androgen receptors in regulating kisspeptin signaling. Conclusion This study provides a detailed chemoanatomical map of kisspeptin-expressing neurons in the brain, highlighting their potential functional diversity. The discovery of new kisspeptin-expressing neuronal populations, and gonadectomy-induced changes in Kiss1 expression patterns, provide a basis for further exploration of non-endocrine roles for kisspeptin in brain function.