PACAP neurons in the ventral premammillary nucleus regulate reproductive function in the female mouse

Rachel A. Ross, Silvia Leon, Joseph C. Madara, Danielle Schafer, Chrysanthi Fergani, Caroline A. Maguire, Anne M.J. Verstegen, Emily Brengle, Dong Kong, Allan E. Herbison, Ursula B. Kaiser, Bradford B. Lowell, Victor M. Navarro

Research output: Contribution to journalArticlepeer-review

54 Scopus citations


Pituitary adenylate cyclase activating polypeptide (PACAP, Adcyap1) is a neuromodulator implicated in anxiety, metabolism and reproductive behavior. PACAP global knockout mice have decreased fertility and PACAP modulates LH release. However, its source and role at the hypothalamic level remain unknown. We demonstrate that PACAP-expressing neurons of the ventral premamillary nucleus of the hypothalamus (PMV PACAP ) project to, and make direct contact with, kisspeptin neurons in the arcuate and AVPV/PeN nuclei and a subset of these neurons respond to PACAP exposure. Targeted deletion of PACAP from the PMV through stereotaxic virally mediated cre-injection or genetic cross to LepR-i-cre mice with Adcyap1 fl/fl mice led to delayed puberty onset and impaired reproductive function in female, but not male, mice. We propose a new role for PACAP-expressing neurons in the PMV in the relay of nutritional state information to regulate GnRH release by modulating the activity of kisspeptin neurons, thereby regulating reproduction in female mice.

Original languageEnglish (US)
Article numbere35960
StatePublished - Jun 15 2018
Externally publishedYes

ASJC Scopus subject areas

  • Neuroscience(all)
  • Biochemistry, Genetics and Molecular Biology(all)
  • Immunology and Microbiology(all)


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