FRI272 Sex-Specific Role Of ProkR2 Neurons Of The Posterior Amygdala In The Integration Of Odors And Neuroendocrine Responses

Abstract

Abstract Disclosure: B. Cisneros-Larios: None. C.F. Elias: None. Kallmann Syndrome (KS) is characterized by abnormal development of the reproductive axis and olfactory bulb dysgenesis. Genetic studies have revealed that Kallmann Syndrome is caused by loss-of-function mutations in several genes including the prokineticin receptor 2 (PROKR2) gene. Prokr2 null mice exhibit the same phenotype of KS patients. While the role of PROKR2 during development has been linked with GnRH neuron migration, limited data exists on PROKR2 neurons in adult reproduction. PROKR2 mRNA are highly expressed in reproductive control sites. Furthermore, our lab previously found sexually dimorphic expression of PROKR2 mRNA and Prokr2-Cre GFP+ cells in several reproductive control sites. The posterior amygdala had higher PROKR2 expression in males compared to female mice. More recently, we identified expression of sex steroid receptors in PROKR2 expressing cells of the PA. The amygdala is an important site of socio-sexual inputs and reproductive neuroendocrine responses in rodents and primates, including humans. We hypothesize Prokr2-Cre neurons in the PA have a role in male reproductive function. Using genetic tracing techniques, we mapped PA Prokr2-Cre neuronal projections in male mice and found dense innervation to reproductive control sites such as the medial preoptic area and the ventral premammillary nucleus. We found activation of these neurons, via fos expression, after opposite sex soiled bedding exposure (olfactory cues). Lastly, selective activation, using chemogenetic technology DREADDs, of PA Prokr2-Cre cells in males can induce a rise in circulating luteinizing hormone. These data suggest PA Prokr2-Cre cells have a role in pathways integrating olfactory cues and reproductive endocrine responses (e.g., aggression, mating behavior). We expect our studies will contribute to the understanding of the role of PROKR2 neurons in adult reproduction and reproductive deficits associated with PROKR2 mutations. Presentation: Friday, June 16, 2023