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

Pituitary adenylate cyclase activating polypeptide (PACAP, ) 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...

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Bibliographic Details
Published in:	eLife Vol. 7
Main Authors:	Ross, Rachel A, Leon, Silvia, Madara, Joseph C, Schafer, Danielle, Fergani, Chrysanthi, Maguire, Caroline A, Verstegen, Anne Mj, Brengle, Emily, Kong, Dong, Herbison, Allan E, Kaiser, Ursula B, Lowell, Bradford B, Navarro, Victor M
Format:	Journal Article
Language:	English
Published:	England eLife Science Publications, Ltd 15-06-2018 eLife Sciences Publications, Ltd eLife Sciences Publications Ltd
Subjects:	Animals Brain Female Gonadotropin-Releasing Hormone - metabolism hypothalamus kisspeptin Kisspeptins - genetics Kisspeptins - metabolism Leptin Male Mice, Inbred C57BL Mice, Knockout Mice, Transgenic Neural circuitry Neurons Neurons - cytology Neurons - metabolism Neuroscience PACAP Physiological aspects Pituitary Adenylate Cyclase-Activating Polypeptide - genetics Pituitary Adenylate Cyclase-Activating Polypeptide - metabolism Polypeptides Receptors, Leptin - genetics Receptors, Leptin - metabolism reproduction Reproduction - genetics Reproduction - physiology Sex Factors Sexual Maturation - genetics Ventromedial Hypothalamic Nucleus - cytology Ventromedial Hypothalamic Nucleus - metabolism mouse PACAP kisspeptin neuroscience hypothalamus reproduction
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Summary:	Pituitary adenylate cyclase activating polypeptide (PACAP, ) 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 ) 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 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.
Bibliography:	ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 23
ISSN:	2050-084X 2050-084X
DOI:	10.7554/elife.35960