Role of extra-hypothalamic kisspeptin and GnRH in memory retention in mice

Kisspeptin is a neuropeptide known for its crucial role in the hypothalamic-pituitary-gonadal axis (HPG) that controls reproductive function. The populations of kisspeptin neurons are located in the hypothalamus, more precisely in the anteroventral periventricular area (AVPV) and arcuate nucleus (ARC). Both modulates the pulsatile release of GnRH, responsible for the pre-ovulatory peak of LH. Interestingly, the kisspeptin receptor, GPR54, is present in extra-hypothalamic areas such as the cortex and hippocampus among others. These observations suggest that kisspeptin and GPR54 may play a role in non-reproductive functions such as cognition, mood or social behaviors. Therefore, we propose to study the role of kisspeptine and GnRH in mouse memory. First, the injection of a retrograde viral vector in Kiss::Cre mice show that the AVPV and the ARC kisspeptin neurons population project to the dorsal region CA1 of the hippocampus. Then, we administered the female wild-type mice with kisspeptine or GnRH and performed on these mice the new object recognition test (NOR) which allows to evaluate memory retention. Administration of these two drugs showed a significant increase in memory performance in these mice. Finally, by using chemogenetic method, we injected a viral vector allowing the expression of hM4Di in the AVPV nucleus in Kiss mice:Cre to specifically inhibit the AVPV kisspeptin neurons. These mice showed significantly decreased memory retention performance compared to the controls. Together, these results suggest that kisspeptine and the GnRH play a role in memory formation and retention.