Comprehensive chemoanatomical mapping, and the gonadal regulation, of seven kisspeptin neuronal populations in the mouse brain

Kisspeptinergic signaling is well-established as crucial for the 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. RNAscope single, dual, 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 wild-type intact and gonadectomized young adult mice. Seven distinct kisspeptin neuronal chemotypes were characterized, including two novel kisspeptin-expressing groups described for the first time, that is, the Kiss1 population in the ventral premammillary nucleus and the nucleus of the solitary tract. Kiss1 mRNA was also observed to localize in both somatic and dendritic compartments of hypothalamic neurons. High androgen receptor expression and changes in medial amygdala and septo-hypothalamic Kiss1 expression following GDX in males, but not in females, suggest a role for androgen receptors in regulating kisspeptin signaling. This study provides a detailed chemoanatomical map of kisspeptin-expressing neurons, highlighting their potential functional diversity. The discovery of a new kisspeptin-expressing group and gonadectomy-induced changes in Kiss1 expression patterns suggest broader roles for kisspeptin in brain functions beyond those of reproduction.