Skip to main content
SpringerLink
Log in

Somato-Dendritic Secretion of Neuropeptides

  • Chapter
  • First Online:
Neurosecretion: Secretory Mechanisms

Part of the book series: Masterclass in Neuroendocrinology ((MANEURO,volume 8))

  • 570 Accesses

Abstract

In addition to classical neurosecretion at the synapse, many neurons also secrete neurotransmitters from their cell bodies and dendrites. In contrast to synaptic transmission, somato-dendritic secretion is best characterized as modulating the overall excitability of the target cells over a longer time course via actions at presynaptic and extrasynaptic receptors. Magnocellular neurons of the hypothalamic supraoptic and paraventricular nuclei synthesize the neuropeptides, vasopressin and oxytocin, and were among the first neurons shown to secrete neurotransmitters from their cell bodies and dendrites by exocytosis. These neuropeptides modulate the activity of the neurons from which they are secreted, as well as the activity of neighboring neurons, to provide intra- and interpopulation signals that coordinate the endocrine and autonomic responses for control of cardiovascular and reproductive physiology, as well as behavior.

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

Access this chapter

Log in via an institution
Chapter
USD 29.95
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
eBook
USD 84.99
Price excludes VAT (USA)
  • Available as EPUB and PDF
  • Read on any device
  • Instant download
  • Own it forever
Softcover Book
USD 109.99
Price excludes VAT (USA)
  • Compact, lightweight edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info
Hardcover Book
USD 109.99
Price excludes VAT (USA)
  • Durable hardcover edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info

Tax calculation will be finalised at checkout

Purchases are for personal use only

Institutional subscriptions

Change history

  • 11 June 2020

    The original version of Chapter 4 was inadvertently published with only the second affiliation of the author Mike Ludwig, but his first affiliation was missing. This has now been corrected.

References

  • Augustine RA, Seymour AJ, Campbell RE, Grattan DR, Brown CH (2018) Integrative neuro-humoral regulation of oxytocin neuron activity in pregnancy and lactation. J Neuroendocrinol 30:e12569. https://doi.org/10.1111/jne.12569

    Article  CAS  Google Scholar 

  • Bains JS, Ferguson AV (1999) Activation of N-methyl-D-aspartate receptors evokes calcium spikes in the dendrites of rat hypothalamic paraventricular nucleus neurons. Neuroscience 90:885–891

    Article  CAS  PubMed  Google Scholar 

  • Belin V, Moos F, Richard P (1984) Synchronization of oxytocin cells in the hypothalamic paraventricular and supraoptic nuclei in suckled rats: direct proof with paired extracellular recordings. Exp Brain Res 57:201–203

    Article  CAS  PubMed  Google Scholar 

  • Blackburn-Munro G, Brown CH, Neumann ID, Landgraf R, Russell JA (2000) Verapamil prevents withdrawal excitation of oxytocin neurones in morphine-dependent rats. Neuropharmacology 39:1596–1607

    Article  CAS  PubMed  Google Scholar 

  • Brown CH (2016) Magnocellular neurons and posterior pituitary function. Compr Physiol 6:1701–1741

    Article  PubMed  Google Scholar 

  • Brown CH, Bourque CW (2004) Autocrine feedback inhibition of plateau potentials terminates phasic bursts in magnocellular neurosecretory cells of the rat supraoptic nucleus. J Physiol 557:949–960

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Brown CH, Russell JA (2004) Cellular mechanisms underlying neuronal excitability during morphine withdrawal in physical dependence: lessons from the magnocellular oxytocin system. Stress 7:97–107

    Article  CAS  PubMed  Google Scholar 

  • Brown CH, Munro G, Johnstone LE, Robson AC, Landgraf R, Russell JA (1997) Oxytocin neurone autoexcitation during morphine withdrawal in anaesthetized rats. Neuroreport 8:951–955

    Article  CAS  PubMed  Google Scholar 

  • Brown CH, Murphy NP, Munro G, Ludwig M, Bull PM, Leng G, Russell JA (1998) Interruption of central noradrenergic pathways and morphine withdrawal excitation of oxytocin neurones in the rat. J Physiol 507:831–842

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Brown CH, Scott V, Ludwig M, Leng G, Bourque CW (2007) Somatodendritic dynorphin release: orchestrating activity patterns of vasopressin neurons. Biochem Soc Trans 35:1236–1242

    Article  CAS  PubMed  Google Scholar 

  • Brown CH, Ruan M, Scott V, Tobin VA, Ludwig M (2008) Multi-factorial somato-dendritic regulation of phasic spike discharge in vasopressin neurons. Prog Brain Res 170:219–228

    Article  CAS  PubMed  Google Scholar 

  • Brown CH, Bains JS, Ludwig M, Stern JE (2013) Physiological regulation of magnocellular neurosecretory cell activity: integration of intrinsic, local and afferent mechanisms. J Neuroendocrinol 25:678–710

    Article  CAS  PubMed  Google Scholar 

  • Dayanithi G, Sabatier N, Widmer H (2000) Intracellular calcium signalling in magnocellular neurones of the rat supraoptic nucleus: understanding the autoregulatory mechanisms. Exp Physiol 85(Spec No):75S

    Google Scholar 

  • Dayanithi G, Forostyak O, Ueta Y, Verkhratsky A, Toescu EC (2012) Segregation of calcium signalling mechanisms in magnocellular neurones and terminals. Cell Calcium 51:293–299

    Article  CAS  PubMed  Google Scholar 

  • de Kock CP, Wierda KD, Bosman LW, Min R, Koksma JJ, Mansvelder HD, Verhage M, Brussaard AB (2003) Somatodendritic secretion in oxytocin neurons is upregulated during the female reproductive cycle. J Neurosci 23:2726–2734

    Article  PubMed  PubMed Central  Google Scholar 

  • de Kock CP, Burnashev N, Lodder JC, Mansvelder HD, Brussaard AB (2004) NMDA receptors induce somatodendritic secretion in hypothalamic neurones of lactating female rats. J Physiol 561:53–64

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Doi N, Brown CH, Cohen HD, Leng G, Russell JA (2001) Effects of the endogenous opioid peptide, endomorphin 1, on supraoptic nucleus oxytocin and vasopressin neurones in vivo and in vitro. Br J Pharmacol 132:1136–1144

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Gouzenes L, Desarmenien MG, Hussy N, Richard P, Moos FC (1998) Vasopressin regularizes the phasic firing pattern of rat hypothalamic magnocellular vasopressin neurons. J Neurosci 18:1879–1885

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Hermes ML, Ruijter JM, Klop A, Buijs RM, Renaud LP (2000) Vasopressin increases GABAergic inhibition of rat hypothalamic paraventricular nucleus neurons in vitro. J Neurophysiol 83:705–711

    Article  CAS  PubMed  Google Scholar 

  • Hirasawa M, Schwab Y, Natah S, Hillard CJ, Mackie K, Sharkey KA, Pittman QJ (2004) Dendritically released transmitters cooperate via autocrine and retrograde actions to inhibit afferent excitation in rat brain. J Physiol 559:611–624

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Hurbin A, Orcel H, Alonso G, Moos F, Rabie A (2002) The vasopressin receptors colocalize with vasopressin in the magnocellular neurons of the rat supraoptic nucleus and are modulated by water balance. Endocrinology 143:456–466

    Article  CAS  PubMed  Google Scholar 

  • Iremonger KJ, Bains JS (2009) Retrograde opioid signaling regulates glutamatergic transmission in the hypothalamus. J Neurosci 29:7349–7358

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Knobloch HS, Charlet A, Hoffmann LC, Eliava M, Khrulev S, Cetin AH, Osten P, Schwarz MK, Seeburg PH, Stoop R, Grinevich V (2012) Evoked axonal oxytocin release in the central amygdala attenuates fear response. Neuron 73:553–566

    Article  CAS  PubMed  Google Scholar 

  • Kombian SB, Mouginot D, Hirasawa M, Pittman QJ (2000) Vasopressin preferentially depresses excitatory over inhibitory synaptic transmission in the rat supraoptic nucleus in vitro. J Neuroendocrinol 12:361–367

    Article  CAS  PubMed  Google Scholar 

  • Landgraf R, Neumann I, Schwarzberg H (1988) Central and peripheral release of vasopressin and oxytocin in the conscious rat after osmotic stimulation. Brain Res 457:219

    Article  CAS  PubMed  Google Scholar 

  • Landry M, Vila-Porcile E, Hokfelt T, Calas A (2003) Differential routing of coexisting neuropeptides in vasopressin neurons. Eur J Neurosci 17:579–589

    Article  PubMed  Google Scholar 

  • Leng G, Sabatier N (2017) Oxytocin—the sweet hormone? Trends Endocrinol Metab 28:365–376

    Article  CAS  PubMed  Google Scholar 

  • Leng G, Ludwig M, Douglas AJ (2012) Neural control of the posterior pituitary gland (neurohypophysis). In: Fink G, Pfaff DW, Levine JE (eds) Handbook of Neuroendocrinology. Academic, London

    Google Scholar 

  • Ludwig M, Leng G (1997) Autoinhibition of supraoptic nucleus vasopressin neurons in vivo: a combined retrodialysis/electrophysiological study in rats. Eur J Neurosci 9:2532–2540

    Article  CAS  PubMed  Google Scholar 

  • Ludwig M, Leng G (2006) Dendritic peptide release and peptide-dependent behaviours. Nat Rev Neurosci 7:126–136

    Article  CAS  PubMed  Google Scholar 

  • Ludwig M, Callahan MF, Neumann I, Landgraf R, Morris M (1994) Systemic osmotic stimulation increases vasopressin and oxytocin release within the supraoptic nucleus. J Neuroendocrinol 6:369–373

    Article  CAS  PubMed  Google Scholar 

  • Ludwig M, Sabatier N, Bull PM, Landgraf R, Dayanithi G, Leng G (2002) Intracellular calcium stores regulate activity-dependent neuropeptide release from dendrites. Nature 418:85–89

    Article  CAS  PubMed  Google Scholar 

  • Ludwig M, Bull PM, Tobin VA, Sabatier N, Landgraf R, Dayanithi G, Leng G (2005) Regulation of activity-dependent dendritic vasopressin release from rat supraoptic neurones. J Physiol 564:515–522

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Ludwig M, Apps D, Menzies J, Patel JC, Rice ME (2017) Dendritic release of neurotransmitters. Compr Physiol 7:235–252

    Google Scholar 

  • Mcgregor IS, Bowen MT (2012) Breaking the loop: oxytocin as a potential treatment for drug addiction. Horm Behav 61:331–339

    Article  CAS  PubMed  Google Scholar 

  • Moos F, Poulain DA, Rodriguez F, Guerne Y, Vincent JD, Richard P (1989) Release of oxytocin within the supraoptic nucleus during the milk ejection reflex in rats. Exp Brain Res 76:593–602

    Article  CAS  PubMed  Google Scholar 

  • Morris JF, Pow DV (1991) Widespread release of peptides in the central nervous system: quantitation of tannic acid-captured exocytoses. Anat Rec 231:437–445

    Article  CAS  PubMed  Google Scholar 

  • Pow DV, Morris JF (1989) Dendrites of hypothalamic magnocellular neurons release neurohypophysial peptides by exocytosis. Neuroscience 32:435–439

    Article  CAS  PubMed  Google Scholar 

  • Ross HE, Young LJ (2009) Oxytocin and the neural mechanisms regulating social cognition and affiliative behavior. Front Neuroendocrinol 30:534–547

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Sabatier N, Leng G (2006) Presynaptic actions of endocannabinoids mediate alpha-MSH-induced inhibition of oxytocin cells. Am J Physiol Regul Integr Comp Physiol 290:R577–R584

    Article  CAS  PubMed  Google Scholar 

  • Sabatier N, Caquineau C, Dayanithi G, Bull P, Douglas AJ, Guan XM, Jiang M, Van der Ploeg L, Leng G (2003) Alpha-melanocyte-stimulating hormone stimulates oxytocin release from the dendrites of hypothalamic neurons while inhibiting oxytocin release from their terminals in the neurohypophysis. J Neurosci 23:10351–10358

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Scott V, Brown CH (2010) State-dependent plasticity in vasopressin neurones: dehydration-induced changes in activity patterning. J Neuroendocrinol 22:343–354

    Article  CAS  PubMed  Google Scholar 

  • Scott V, Bishop VR, Leng G, Brown CH (2009) Dehydration-induced modulation of kappa-opioid inhibition of vasopressin neurone activity. J Physiol 587:5679–5689

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Shuster SJ, Riedl M, Li X, Vulchanova L, Elde R (2000) The kappa opioid receptor and dynorphin co-localize in vasopressin magnocellular neurosecretory neurons in guinea-pig hypothalamus. Neuroscience 96:373–383

    Article  CAS  PubMed  Google Scholar 

  • Son SJ, Filosa JA, Potapenko ES, Biancardi VC, Zheng H, Patel KP, Tobin VA, Ludwig M, Stern JE (2013) Dendritic peptide release mediates interpopulation crosstalk between neurosecretory and preautonomic networks. Neuron 78:1036–1049

    Article  CAS  PubMed  Google Scholar 

  • Stern JE (2015) Neuroendocrine-autonomic integration in the paraventricular nucleus: novel roles for dendritically released neuropeptides. J Neuroendocrinol 27:487–497

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Sykova E (2004) Extrasynaptic volume transmission and diffusion parameters of the extracellular space. Neuroscience 129:861–876

    Article  CAS  PubMed  Google Scholar 

  • Takayanagi Y, Yoshida M, Takashima A, Takanami K, Yoshida S, Nishimori K, Nishijima I, Sakamoto H, Yamagata T, Onaka T (2017) Activation of supraoptic oxytocin neurons by secretin facilitates social recognition. Biol Psychiatry 81:243–251

    Article  CAS  PubMed  Google Scholar 

  • Tobin VA, Ludwig M (2007) The role of the actin cytoskeleton in oxytocin and vasopressin release from rat supraoptic nucleus neurons. J Physiol 582:1337–1348

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Tobin VA, Hurst G, Norrie L, Dal Rio FP, Bull PM, Ludwig M (2004) Thapsigargin-induced mobilization of dendritic dense-cored vesicles in rat supraoptic neurons. Eur J Neurosci 19:2909–2912

    Article  PubMed  Google Scholar 

  • Tobin VA, Douglas AJ, Leng G, Ludwig M (2011) The involvement of voltage-operated calcium channels in somato-dendritic oxytocin release. PLoS One 6:e25366

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Tobin V, Schwab Y, Lelos N, Onaka T, Pittman QJ, Ludwig M (2012) Expression of exocytosis proteins in rat supraoptic nucleus neurones. J Neuroendocrinol 24:629–641

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Wang YF, Hatton GI (2005) Burst firing of oxytocin neurons in male rat hypothalamic slices. Brain Res 1032:36–43

    Article  CAS  PubMed  Google Scholar 

Further Recommended Reading

    Somato-Dendritic Secretion

    • Dendritic Neurotransmitter Release (2004) ed. Ludwig, M. pp xvi + 334, Springer, New York. ISBN 10: 0387229337 ISBN 13: 9780387229331

      Google Scholar 

    • Ludwig M, Apps D, Menzies J, Patel JC, Rice ME (2016) Dendritic release of neurotransmitters. Compr Physiol 7:235–252

      Article  PubMed  PubMed Central  Google Scholar 

    Phasic Activity Patterning in Vasopressin Neurons

    • Brown CH, Bourque CW (2006) Mechanisms of rhythmogenesis: insights from hypothalamic vasopressin neurons. Trends Neurosci 29:108–115

      Article  CAS  PubMed  Google Scholar 

    Morphine Dependence in Oxytocin Neurons

    • Brown CH, Russell JA (2004) Cellular mechanisms underlying neuronal excitability during morphine withdrawal in physical dependence: lessons from the magnocellular oxytocin system. Stress 7:97–107

      Article  CAS  PubMed  Google Scholar 

    Inter-Population Signaling

    • Stern JE (2015) Neuroendocrine-autonomic integration in the paraventricular nucleus: novel roles for dendritically released neuropeptides. J Neuroendocrinol 27:487–497

      Article  CAS  PubMed  PubMed Central  Google Scholar 

    Reproductive Regulation of Oxytocin Neuron Activity

    Regulation of Energy Balance by Oxytocin

    Regulation of Social Behavior by Oxytocin

    Download references

    Author information

    Authors and Affiliations

    1. Department of Physiology, Brain Health Research Centre, Centre for Neuroendocrinology, University of Otago, Dunedin, New Zealand

      Colin H. Brown

    2. Centre for Discovery Brain Sciences, The University of Edinburgh, Edinburgh, UK

      Mike Ludwig

    3. Department of Immunology, Centre for Neuroendocrinology, University of Pretoria, Pretoria, South Africa

      Mike Ludwig

    4. Neuroscience Institute, Georgia State University, Atlanta, GA, USA

      Javier E. Stern

    Authors
    1. Colin H. Brown
      View author publications

      You can also search for this author in PubMed Google Scholar

    2. Mike Ludwig
      View author publications

      You can also search for this author in PubMed Google Scholar

    3. Javier E. Stern
      View author publications

      You can also search for this author in PubMed Google Scholar

    Corresponding author

    Correspondence to Colin H. Brown .

    Editor information

    Editors and Affiliations

    1. Medical School, University of Massachusetts, Worcester, MA, USA

      José R. Lemos

    2. Molecular Mechanisms in Neurodegenerative Diseases Laboratory, MMDN, University of Montpellier, EPHE, INSERM, UMR-S1198, Montpellier, France

      Govindan Dayanithi

    4.1 Key References: See Main List for Reference Details

    • Knobloch et al. (2012) Demonstration of axon collaterals from magnocellular neurons that project to the central amygdala and nucleus accumbens; oxytocin (and glutamate) release from the collaterals in the central amygdala were shown to modulate fear conditioning and the collaterals to the nucleus accumbens presumably modulate the brain reward pathway.

    • Ludwig and Leng (1997) First demonstration of somato-dendritic secretion of vasopressin inhibiting action potential firing in magnocellular neurons. Inta-supraoptic nucleus administration of a V1-receptor antagonist increased the firing rate of phasic vasopressin neurons, showing that endogenous vasopressin is autoinhibitory.

    • Pow and Morris (1989) First demonstration somato-dendritic exocytosis of dense core vesicles from magnocellular neurons.

    • Son et al. (2013) First unequivocal demonstration that somato-dendritic neuropeptide secretion from magnocellular neurons have direct paracrine effects to modulate action potential firing of neighboring non-magnocellular neurons.

    • Takayanagi et al. (2017) First direct evidence showing oxytocin release from magnocellular neuron dendrites (some of which were shown to course near/into the medial amygdala) affects neuronal populations outside the supraoptic and paraventricular nuclei.

    4.1 Extra Supplementary Material

    Movie 4.1

    In vivo extracellular single-unit recording from the supraoptic nucleus with microdialysis drug application in anesthetized rats. Urethane-anesthetized rats are placed supine in a stereotaxic frame. The ventral surface of the brain is exposed through the oral and nasal cavities. A U-shaped microdialysis probe is placed over the surface of the supraoptic nucleus for drug administration. A recording micropipette is placed into the supraoptic nucleus through the center of the dialysis loop. A stimulating electrode is placed on the neural stalk where magnocellular axons gather together before the arrival at the posterior pituitary gland. The stimulator is used to evoke an antidromic spike with a constant latency that is recorded at the supraoptic nucleus. Once the neuron is identified as projecting to the posterior pituitary gland, the stimulator is switched off and the spontaneous activity is recorded before and during drug administration via the dialysis probe (WMV 1161 kb)

    Rights and permissions

    Reprints and permissions

    Copyright information

    © 2020 Springer Nature Switzerland AG

    About this chapter

    Check for updates. Verify currency and authenticity via CrossMark

    Cite this chapter

    Brown, C.H., Ludwig, M., Stern, J.E. (2020). Somato-Dendritic Secretion of Neuropeptides. In: Lemos, J., Dayanithi, G. (eds) Neurosecretion: Secretory Mechanisms. Masterclass in Neuroendocrinology, vol 8. Springer, Cham. https://doi.org/10.1007/978-3-030-22989-4_4

    Download citation

    Publish with us

    Policies and ethics

    Search

    Navigation