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

Herein, we present a systematic analysis, using dual and multiplex RNAscope methods, of seven kisspeptinergic neuronal populations, based on their chemotyping and distribution throughout the mouse brain. The co-expression of mRNAs coding for neuropeptides, for excitatory and inhibitory transmitter vesicular transporters, and for sex steroid receptors are described in four hypothalamic and three extra-hypothalamic nuclei. These include a newly characterized kisspeptin-expressing ventral premammillary nucleus cell group co-expressing vesicular glutamate transporter 2, pituitary adenylate cyclase-activating polypeptide and neurotensin mRNAs. Kisspeptin mRNA ( Kiss1) was observed within both somatic and dendritic compartments at a single-cell level in two hypothalamic sites, a prominent and previously undescribed feature of kisspeptin neurons in these two cell groups. Patterns of altered Kiss1 expression following gonadectomy among these seven KP populations suggest that androgen receptor signaling may also play a previously unremarked role in gonadal feedback regulation of kisspeptinergic neuronal function. Data from this study provide a chemoanatomical basis for hypothesis generation regarding the functional diversity of kisspeptinergic signaling in hypothalamic and extrahypothalamic brain.