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New determinants of firing rates and patterns of vasopressinergic magnocellular neurons: predictions using a mathematical model of osmodetection

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Abstract

Arginine vasopressin (AVP), one of the most important hormones involved in hydromineral homeostasis, is secreted by hypothalamic magnocellular neurons (MCNs). Here, we implemented two critical parameters for MCN physiology into a Hodgkin-Huxley simulation of the MCN. By incorporating the mechanosensitive channel (MSC) responsible for osmodetection and the synaptic inputs whose frequencies are modulated by changes in ambient osmolality into our model, we were able to develop an improved model with increased physiological relevance and gain new insight into the determinants of the firing patterns of AVP magnocellular neurons. Our results with this MCN model predict that 1) a single MCN is able to display all the firing patterns experimentally observed: silent, irregular, phasic and continuous firing patterns; 2) under conditions of hyperosmolality, burst durations are regulated by the frequency-dependent fatigue of dynorphin secretion; and 3) the transitions between firing patterns are controlled by EPSP and IPSP frequencies (0, 2, 4, 8, 16, 32, 64 and 128 Hz). Moreover, this simulation predicts that EPSPs and IPSPs do not modify the spiking frequency (SF) of phasic firing patterns (0.0034 Hz/Hz [EPSP]; 0.0012 Hz/Hz [IPSP]). Rather, these afferents strongly regulate SF during irregular and continuous firing patterns (0.075 Hz/Hz [EPSP]; 0.027 Hz/Hz [IPSP]). The use of the realistic MCN model developed here allows for an improved understanding of the determinants driving the firing patterns and spiking frequencies of vasopressinergic magnocellular neurons.

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Acknowledgement

This project was supported by the Canadian Institutes for Health Research (CIHR) MOP-178002. LN received a scholarship from the Natural Sciences and Engineering Research Council of Canada (NSERC, ESD3-334440-2006).

We would like to thank Myriam Rioux (University of Ottawa, Canada) and Francis Gagnon-Moisan (PTB, Braunschweig, Germany) for valuable suggestions and comments on the study. We also thank Dr. Charles Bourque (McGill University, Montreal, Canada) for his kind gift of experimental data and for his permission to include these data in the present study. Finally, we would to thank Dr. Peter Roper (The University of Utah, U.S.A.) for sharing his source code and for the useful answers to our questions.

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Authors and Affiliations

  1. Neurosciences and Université Laval, Centre de recherche du CHUQ (CHUL), Québec, G1V 4G2, Canada

    Louis Nadeau & Didier Mouginot

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  1. Louis Nadeau
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  2. Didier Mouginot
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Correspondence to Didier Mouginot.

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Action Editor: Bard Ermentrout

Electronic supplementary material

Below is the link to the electronic supplementary material.

Online Resource 1

Calculation of the MSC conductance as a function of the external osmolality (PDF 394 kb)

Online Resource 2

Adjustment of the Na+ and K+ leak conductance in the MSC model (PDF 181 kb)

Online Resource 3

Comparison of the MCN firing pattern induced by either an increased osmolality, or an increased [Na+]. (PDF 218 kb)

Online Resource 4

Interspike interval histogram of MCNs displaying a phasic firing pattern (PDF 460 kb)

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Nadeau, L., Mouginot, D. New determinants of firing rates and patterns of vasopressinergic magnocellular neurons: predictions using a mathematical model of osmodetection. J Comput Neurosci 31, 441–451 (2011). https://doi.org/10.1007/s10827-011-0321-4

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  • DOI: https://doi.org/10.1007/s10827-011-0321-4

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