Skip to main content
SpringerLink
Log in

Quantitative prediction of vasopressin secretion using a computational population model of rat magnocellular neurons

  • Published:
Journal of Computational Neuroscience Aims and scope Submit manuscript

Abstract

The goal of this study was to create a realistic and quantitative simulation of vasopressin (AVP) secretion under iso-osmotic and short-term challenged plasma osmolality. The relationship between AVP concentration ([AVP]) and plasma osmolality was computed using a sophisticated and integrated model that chronologically simulates (1) the overall firing rate of the hypothalamus’ magnocellular neuronal (MCN) population, (2) the propagation of the spike activity down the axons, (3) the fatigue and facilitation mechanisms of AVP release at the axon terminals and (4) the [AVP] pharmacodynamics based on the trains of AVP release. This global simulation predicted that the differential MCN sensitivity to dynorphin would be the most critical mechanism underlying the individual variability of MCN firing behaviors (silence, irregular, phasic and continuous firing patterns). However, at the level of the MCN population, the simulation predicted that the dynorphin factor must be combined with the distribution of the resting membrane potentials among the MCNs to obtain a realistic overall firing rate in response to a change in osmolality. Moreover, taking advantage of the integrated model, the simulation predicted that the selective removal of the frequency-dependent facilitation of AVP secretion has a major impact on the overall [AVP]-to-osmolality relationship (mean absolute change of 2.59 pg/ml); the action potential propagation failure, while critical, has a smaller quantitative impact on the overall [AVP] (0.58 pg/ml). The present integrated model (from a single MCN to a quantitative plasma [AVP]) improves our knowledge of the mechanisms underlying overall MCN firing and AVP excitation-secretion coupling.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2
Fig. 3
Fig. 4
Fig. 5

Similar content being viewed by others

References

  • Bicknell, R. J. (1988). Optimizing release from peptide hormone secretory nerve terminals. Journal of Experimental Biology, 139, 51–65.

    PubMed  CAS  Google Scholar 

  • Bicknell, R. J., Brown, D., Chapman, C., Hancock, P. D., & Leng, G. (1984). Reversible fatigue of stimulus-secretion coupling in the rat neurohypophysis. Journal of Physiology (London), 348, 601–613.

    CAS  Google Scholar 

  • Bielefeldt, K., & Jackson, M. B. (1993). A calcium-activated potassium channel causes frequency-dependent action-potential failures in a mammalian nerve terminal. Journal of Neurophysiology, 70, 284–298.

    PubMed  CAS  Google Scholar 

  • Bondy, C. A., Gainer, H., & Russell, J. T. (1987). Effects of stimulus frequency and potassium channel blockade on the secretion of vasopressin and oxytocin from the neurohypophysis. Neuroendocrinology, 46, 258–267.

    Article  PubMed  CAS  Google Scholar 

  • Bourque, C. W. (1998). Osmoregulation of vasopressin neurons: a synergy of intrinsic and synaptic processes. Progress in Brain Research, 119, 59–76.

    Article  PubMed  CAS  Google Scholar 

  • Bourque, C. W., & Renaud, L. P. (1991). Membrane properties of rat magnocellular neuroendocrine cells in vivo. Brain Research, 540, 349–352.

    Article  PubMed  CAS  Google Scholar 

  • Brimble, M. J., & Dyball, R. E. (1977). Characterization of the responses of oxytocin- and vasopressin-secreting neurones in the supraoptic nucleus to osmotic stimulation. Journal of Physiology (London), 271, 253–271.

    CAS  Google Scholar 

  • Brown, C. H., Ludwig, M., & Leng, G. (1998). kappa-opioid regulation of neuronal activity in the rat supraoptic nucleus in vivo. Journal of Neuroscience, 18, 9480–9488.

    PubMed  CAS  Google Scholar 

  • Brown, C. H., Ruan, M., Scott, V., Tobin, V. A., & Ludwig, M. (2008). Multi-factorial somato-dendritic regulation of phasic spike discharge in vasopressin neurons. Progress in Brain Research, 170, 219–228.

    Article  PubMed  CAS  Google Scholar 

  • Cazalis, M., Dayanithi, G., & Nordmann, J. J. (1985). The role of patterned burst and interburst interval on the excitation-coupling mechanism in the isolated rat neural lobe. Journal of Physiology (London), 369, 45–60.

    CAS  Google Scholar 

  • Clayton, T. F., Murray, A. F., & Leng, G. (2010). Modeling the in vivo spike activity of phasically-firing vasopressin cells. Journal of Neuroendocrinology, 22, 1290–1300.

    Article  PubMed  CAS  Google Scholar 

  • Czaczkes, J. W., & Kleeman, C. R. (1964). The effects of various states of hydration and the plasma concentration on the turnover of antidiuretic hormone in mammals. Journal of Clinical Investigation, 43, 1649–1658.

    Article  PubMed  CAS  Google Scholar 

  • Dunn, F. L., Brennan, T. J., Nelson, A. E., & Robertson, G. L. (1973). The role of blood osmolality and volume in regulating vasopressin secretion in the rat. Journal of Clinical Investigation, 52, 3212–3219.

    Article  PubMed  CAS  Google Scholar 

  • Dyball, R. E., Grossmann, R., Leng, G., & Shibuki, K. (1988). Spike propagation and conduction failure in the rat neural lobe. Journal of Physiology (London), 401, 241–256.

    CAS  Google Scholar 

  • Hobbach, H., Hurth, S., Jost, D., & Racké, K. (1988). Effects of tetraethylammonium ions on frequency-dependent vasopressin release from the rat neurohypophysis. Journal of Physiology (London), 397, 539–554.

    CAS  Google Scholar 

  • Iremonger, K. J., & Bains, J. S. (2007). Integration of asynchronously released quanta prolongs the postsynaptic spike window. Journal of Neuroscience, 27, 6684–6691.

    Article  PubMed  CAS  Google Scholar 

  • Jackson, M. B., Konnerth, A., & Augustine, G. J. (1991). Action potential broadening and frequency-dependent facilitation of calcium signals in pituitary nerve terminals. Proceedings of the National Academy of Sciences of the United States of America, 88, 380–384.

    Article  PubMed  CAS  Google Scholar 

  • Komandantov, A. O., Trayanova, N. A., & Tasker, J. G. (2007). Somato-dendritic mechanisms underlying the electrophysiological properties of hypothalamic magnocellular neuroendocrine cells: a multicompartmental model study. Journal of Computational Neuroscience, 23, 143–168.

    Article  Google Scholar 

  • Leng, G., & Ludwig, M. (2008). Neurotransmitters and peptides: whispered secrets and public announcements. Journal of Physiology (London), 586, 5625–5632.

    Article  CAS  Google Scholar 

  • Leng, G., Brown, C., Sabatier, N., & Scott, V. (2008a). Population dynamics in vasopressin cells. Neuroendocrinology, 88, 160–172.

    Article  PubMed  CAS  Google Scholar 

  • Leng, G., Onaka, T., Caquineau, C., Sabatier, N., Tobin, V. A., & Takayanagi, Y. (2008b). Oxytocin and appetite. Progress in Brain Research, 170, 137–151.

    Article  PubMed  CAS  Google Scholar 

  • Mason, W. T. (1983). Electrical properties of neurons recorded from the rat supraoptic nucleus in vitro. Proceedings of the Royal Society B: Biological Sciences, 217, 141–161.

    Article  CAS  Google Scholar 

  • Morris, J. F. (1976). Hormone storage in individual neurosecretory granules of the pituitary gland: a quantitative ultrastructural approach to hormone storage in the neural lobe. Journal of Endocrinology, 68, 209–224.

    Article  PubMed  CAS  Google Scholar 

  • Nadeau, L., & Mouginot, D. (2011). New determinants of firing rates and patterns of vasopressinergic magnocellular neurons: predictions using a mathematical model of osmodetection. Journal of Computational Neuroscience, 31, 441–451.

    Article  PubMed  Google Scholar 

  • Nadeau, L., Arbour, D., & Mouginot, D. (2010). Computational simulation of vasopressin secretion using a rat model of the water and electrolyte homeostasis. BMC Physiology, 10, 17.

    Article  PubMed  Google Scholar 

  • Nordmann, J. J., & Stuenkel, E. L. (1986). Electrical properties of axons and neurohypophysial nerve terminals and their relationship to secretion in the rat. The Journal of Physiology (London), 380, 521–539.

    CAS  Google Scholar 

  • Poulain, D. A., Brown, D., & Wakerley, J. (1988). Statistical analysis of patterns of electrical activity in vasopressin and oxytocin-secreting neurones. In: Pulsatility in neuroendocrine systems (ed. Leng G), 119–154. CRC Press, Boca Raton, FL, U.S.A

  • Richard, D., & Bourque, C. W. (1995). Synaptic control of rat supraoptic neurones during osmotic stimulation of the organum vasculosum lamina terminalis in vitro. The Journal of Physiology (London), 489, 567–577.

    CAS  Google Scholar 

  • Roper, P., Callaway, J., & Armstrong, W. (2004). Burst initiation and termination in phasic vasopressin cells of the rat supraoptic nucleus: a combined mathematical, electrical, and calcium fluorescence study. Journal of Neuroscience, 24, 4818–4831.

    Article  PubMed  CAS  Google Scholar 

  • Scott, V., Bishop, V. R., Leng, G., & Brown, C. H. (2009). Dehydration-induced modulation of kappa-opioid inhibition of vasopressin neurone activity. Journal of Physiology (London), 587, 5679–5689.

    Article  CAS  Google Scholar 

  • Verbalis, J. G. (2003). Disorders of body water homeostasis. Best Practice & Research Clinical Endocrinololgy & Metabolism, 17, 471–503.

    Article  CAS  Google Scholar 

  • Wakerley, J. B., Poulain, D. A., & Brown, D. (1978). Comparison of firing patterns in oxytocin- and vasopressin-releasing neurones during progressive dehydration. Brain Research, 148, 425–440.

    Article  PubMed  CAS  Google Scholar 

  • Wakerley, J. B., Poulain, D. A., Dyball, R. E., & Cross, B. A. (1975). Activity of phasic neurosecretory cells during haemorrhage. Nature, 258, 82–84.

    Article  PubMed  CAS  Google Scholar 

  • Walters, J. K., & Hatton, G. I. (1974). Supraoptic neuronal activity in rats during five days of water deprivation. Physiology & Behavior, 13, 661–667.

    Article  CAS  Google Scholar 

  • Weisinger, R. S., Burns, P., Eddie, L. W., & Wintour, E. M. (1993). Relaxin alters the plasm a osmolality-arginine vasopressin relationship in the rat. Journal of Endocrinology, 137, 505–510.

    Article  PubMed  CAS  Google Scholar 

  • Wilson, K. C., Weitzman, R. E., & Fisher, D. A. (1978). Arginine vasopressin metabolism in dogs. II. Modeling and system analysis. American Journal of Physiology, 235, E598–605.

    PubMed  CAS  Google Scholar 

Download references

Acknowledgement

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

The authors would like to thank Drs. Colin Brown (University of Otago, Dunedin, New Zealand) and Charles Bourque (McGill University, Montreal, Canada) for their valuable comments and suggestions on the preliminary results of the study.

Author information

Authors and Affiliations

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

    Louis Nadeau & Didier Mouginot

  2. Faculté de médecine, Université Laval, Québec, QC, Canada

    Louis Nadeau & Didier Mouginot

  3. CRCHUL, local RC-9800, 2705 boulevard Laurier, Québec, QC, G1V 4G2, Canada

    Didier Mouginot

Authors
  1. Louis Nadeau
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Didier Mouginot
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Didier Mouginot.

Additional information

Action Editor: Bard Ermentrout

Electronic supplementary material

Below is the link to the electronic supplementary material.

Online Resource 1

(PDF 45 kb)

Online Resource 2

(PDF 163 kb)

Online Resource 3

(PDF 156 kb)

Online Resource 4

(PDF 240 kb)

Online Resource 5

(PDF 52 kb)

Online Resource 6

(PDF 76 kb)

Rights and permissions

Reprints and permissions

About this article

Cite this article

Nadeau, L., Mouginot, D. Quantitative prediction of vasopressin secretion using a computational population model of rat magnocellular neurons. J Comput Neurosci 33, 533–545 (2012). https://doi.org/10.1007/s10827-012-0399-3

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s10827-012-0399-3

Keywords

Search

Navigation