Kisspeptin neurones in the posterodorsal medial amygdala modulate sexual partner preference and anxiety in male mice

Abstract

The posterodorsal medial amygdala (MePD) is a neural site in the limbic brain involved in regulating emotional and sexual behaviours. There is, however, limited information available on the specific neuronal cell type in the MePD functionally mediating these behaviours in rodents. The recent discovery of a significant kisspeptin neurone population in the MePD has raised interest in the possible role of kisspeptin and its cognate receptor in sexual behaviour. The present study therefore tested the hypothesis that the MePD kisspeptin neurone population is involved in regulating attraction towards opposite sex conspecifics, sexual behaviour, social interaction and the anxiety response by selectively stimulating these neurones using the novel pharmacosynthetic DREADDs (designer receptors exclusively activated by designer drugs) technique. Adult male Kiss‐Cre mice received bilateral stereotaxic injections of a stimulatory DREADD viral construct (AAV‐hSyn‐DIO‐hM3D(Gq)‐mCherry) targeted to the MePD, with subsequent activation by i.p. injection of clozapine‐N‐oxide (CNO). Socio‐sexual behaviours were assessed in a counter‐balanced fashion after i.p. injection of either saline or CNO (5 mg kg‐1). Selective activation of MePD kisspeptin neurones by CNO significantly increased the time spent by male mice in investigating an oestrous female, as well as the duration of social interaction. Additionally, after CNO injection, the mice appeared less anxious, as indicated by a longer exploratory time in the open arms of the elevated plus maze. However, levels of copulatory behaviour were comparable between CNO and saline‐treated controls. These data indicate that DREADD‐induced activation of MePD kisspeptin neurones enhances both sexual partner preference in males and social interaction and also decreases anxiety, suggesting a key role played by MePD kisspeptin in sexual motivation and social behaviour.

Optogenetic stimulation of kisspeptin neurones within the posterodorsal medial amygdala increases luteinising hormone pulse frequency in female mice

“…Our previous study using pharmacological activation of MePD Kiss1 neurones with the DREADD (Designer Receptors Exclusively Activated by Designer Drugs) methodology built upon previous understanding of the facilitatory role of the MePD in sexual behaviour. We showed that stimulating MePD Kiss1 neurones in this way produces a dual result of augmenting sexual partner preference at the same time as attenuating anxiety behaviour in male mice . Furthermore, in studies of men viewing sexual images, i.v.…”

“…The finding of extra‐hypothalamic Kiss1 expression and its receptor in the medial amygdala, and more specifically its posterodorsal subnucleus (MePD), has opened up new possibilities concerning its role in reproductive function. Indeed, we have shown that the MePD Kiss1 neurones are a key upstream regulator of pubertal timing, sexual motivation and social behaviour . Moreover, we have discovered through neuropharmacological studies that kisspeptin signalling in the MePD per se robustly regulates hypothalamic GnRH pulse generator frequency, although the underlying neural mechanisms are unknown.…”

“…Indeed, we have shown that the MePD Kiss1 neurones are a key upstream regulator of pubertal timing, 10 sexual motivation and social behaviour. 11 Moreover, we have discovered through neuropharmacological studies that kisspeptin signalling in the MePD per se robustly regulates hypothalamic GnRH pulse generator frequency, 12 although the underlying neural mechanisms are unknown.…”

Medial Amygdala <b><i>Kiss1</i></b> Neurons Mediate Female Pheromone Stimulation of Luteinizing Hormone in Male Mice

“…Recent studies have identified MeA Kiss neurons and the POA as regulators of sexual motivation and behaviour in male rodents [15, 16, 44]. Several studies have identified various neuronal types in the POA as key players in mediating male-typical mating and paternal behaviour including neurons expressing oestrogen receptor alpha [45], progesterone receptor [46], and galanin [47].…”

“…Chemogenetic activation of MeA Kiss neurons reduces anxiety and enhances the preference for oestrous females in male mice [15]. Intra-MeA infusions of kisspeptin impact LH levels and lead to increased numbers of ex-copula erections in male rats [16], suggesting that MeA Kiss signalling regulates GnRH release and participates in sexual arousal.…”