PACAP neurons in the ventral premammillary nucleus regulate reproductive function in the female mouse
- Beth Israel Deaconess Medical Center, United States
- Harvard Medical School, United States
- University of Otago, New Zealand
- Brigham and Women's Hospital, United States
- Tufts University School of Medicine, United States
Abstract
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 (PMVPACAP) 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 Adcyap1fl/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.
Data availability
All data generated or analysed during this study are included in the manuscript and supporting files.
Article and author information
Author details
Funding
National Institutes of Health (R01 HD090151-A1)
- Victor M Navarro
National Institutes of Health (P30 DK057521)
- Bradford B Lowell
National Institutes of Health (R01 HD082314)
- Ursula B Kaiser
National Institutes of Health (R01 HD019938)
- Ursula B Kaiser
National Institutes of Health (R00 HD071970)
- Victor M Navarro
National Institutes of Health (5T32HL007374-36)
- Rachel A Ross
National Institutes of Health (R01 DK075632)
- Bradford B Lowell
National Institutes of Health (R01 DK089044)
- Bradford B Lowell
National Institutes of Health (R01 DK111401)
- Bradford B Lowell
National Institutes of Health (P30 DK046200)
- Bradford B Lowell
The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.
Ethics
Animal experimentation: All animal care and experimental procedures were approved by the National Institute of Health, Beth Israel Deaconess Medical Center and Brigham and Women's Hospital Institutional Animal Care and Use Committee . protocol #05165.
Copyright
© 2018, Ross et al.
This article is distributed under the terms of the Creative Commons Attribution License permitting unrestricted use and redistribution provided that the original author and source are credited.
Metrics
-
- 2,632
- views
-
- 437
- downloads
-
- 66
- citations
Views, downloads and citations are aggregated across all versions of this paper published by eLife.
Download links
A two-part list of links to download the article, or parts of the article, in various formats.
Downloads (link to download the article as PDF)
Open citations (links to open the citations from this article in various online reference manager services)
Cite this article (links to download the citations from this article in formats compatible with various reference manager tools)
PACAP neurons in the ventral premammillary nucleus regulate reproductive function in the female mouse
eLife 7:e35960.
https://doi.org/10.7554/eLife.35960
Further reading
-
- Neuroscience
Techniques that enable precise manipulations of subsets of neurons in the fly central nervous system (CNS) have greatly facilitated our understanding of the neural basis of behavior. Split-GAL4 driver lines allow specific targeting of cell types in Drosophila melanogaster and other species. We describe here a collection of 3060 lines targeting a range of cell types in the adult Drosophila CNS and 1373 lines characterized in third-instar larvae. These tools enable functional, transcriptomic, and proteomic studies based on precise anatomical targeting. NeuronBridge and other search tools relate light microscopy images of these split-GAL4 lines to connectomes reconstructed from electron microscopy images. The collections are the result of screening over 77,000 split hemidriver combinations. Previously published and new lines are included, all validated for driver expression and curated for optimal cell-type specificity across diverse cell types. In addition to images and fly stocks for these well-characterized lines, we make available 300,000 new 3D images of other split-GAL4 lines.
-
- Neuroscience
Cell identification is an important yet difficult process in data analysis of biological images. Previously, we developed an automated cell identification method called CRF_ID and demonstrated its high performance in Caenorhabditis elegans whole-brain images (Chaudhary et al., 2021). However, because the method was optimized for whole-brain imaging, comparable performance could not be guaranteed for application in commonly used C. elegans multi-cell images that display a subpopulation of cells. Here, we present an advancement, CRF_ID 2.0, that expands the generalizability of the method to multi-cell imaging beyond whole-brain imaging. To illustrate the application of the advance, we show the characterization of CRF_ID 2.0 in multi-cell imaging and cell-specific gene expression analysis in C. elegans. This work demonstrates that high-accuracy automated cell annotation in multi-cell imaging can expedite cell identification and reduce its subjectivity in C. elegans and potentially other biological images of various origins.
