Dendritic osmosensors modulate activity-induced calcium influx in oxytocinergic magnocellular neurons of the mouse PVN

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Abstract

Hypothalamic oxytocinergic magnocellular neurons have a fascinating ability to release peptide from both their axon terminals and from their dendrites. Existing data indicates that the relationship between somatic activity and dendritic release is not constant, but the mechanisms through which this relationship can be modulated are not completely understood. Here we use a combination of electrical and optical recording techniques to quantify activity-induced calcium influx in proximal vs. distal dendrites of oxytocinergic magnocellular neurons located in the paraventricular nucleus of the hypothalamus (OT-MCNs). Results reveal that the dendrites of OT-MCNs are weak conductors of somatic voltage changes, however activity-induced dendritic calcium influx can be robustly regulated by both osmosensitive and non-osmosensitive ion channels located along the dendritic membrane. Overall, this study reveals that dendritic conductivity is a dynamic and endogenously regulated feature of OT-MCNs that is likely to have substantial functional impact on central oxytocin release.

Data availability

All data generated or analysed during this study are included in the manuscript and supporting files. Source data files have been provided for all figures.

Article and author information

Author details

Wanhui Sheng

Department of Pharmacodynamics, University of Florida, Gainesville, United States

For correspondence
shengwanhui@ufl.edu

Competing interests
The authors declare that no competing interests exist.
Scott W Harden

Department of Pharmacodynamics, University of Florida, Gainesville, United States

For correspondence
swharden@ufl.edu

Competing interests
The authors declare that no competing interests exist.

"This ORCID iD identifies the author of this article:" 0000-0002-0757-1979
Yalun Tan

Department of Pharmacodynamics, University of Florida, Gainesville, United States

For correspondence
yaluntan@stanford.edu

Competing interests
The authors declare that no competing interests exist.
Eric G Krause

Department of Pharmacodynamics, University of Florida, Gainesville, United States

For correspondence
EKrause@cop.ufl.edu

Competing interests
The authors declare that no competing interests exist.
Charles J Frazier

Department of Pharmacodynamics, University of Florida, Gainesville, United States

For correspondence
cjfraz@ufl.edu

Competing interests
The authors declare that no competing interests exist.

"This ORCID iD identifies the author of this article:" 0000-0003-3550-4789

Funding

National Institute of Mental Health (R01MH104641)

Charles J Frazier

National Heart, Lung, and Blood Institute (R01HL122494)

Eric G Krause

The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.

Ethics

Animal experimentation: This study was performed in strict accordance with the recommendations in the Guide for the Care and Use of Laboratory Animals of the National Institutes of Health. All animal procedures were reviewed and approved by the Institutional Animal Care and Use Committee (IACUC) at the University of Florida (under protocol # 201701866).

Copyright

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.