Magnocellular Neurons of the Hypothalamus

Abstract

Magnocellular neurons are neuroendocrine cells located in the hypothalamus; they are among the largest cells in the brain, and synthesise the hormones arginine vasopressin and oxytocin. These neuropeptides are secreted from Magnocellular neuron terminals in the neurohypophysis. It is this hypothalamic–neurohypophysial system which allowed the original formulation of the calcium hypothesis for stimulus–secretion coupling. Vasopressin is a vasoconstrictor and an antidiuretic and, thus, is involved in fluid homeostasis and osmoregulation. Oxytocin has recognised functions in parturition and lactation and has an emerging role as a natriuretic agent. Both hormones may also be central neurotransmitters and have been implicated in stress, social behaviours, learning and memory processes, as well as the development and maintenance of tolerance to ethanol and other drugs of abuse. Furthermore, oxytocin has possible therapeutic applications for social disorders.

Key Concepts

  • Magnocellular neurons in the hypothalamus synthesise the peptide hormones, vasopressin and oxytocin.
  • These neuropeptides are secreted from Magnocellular neuron nerve terminals in the hypothalamic–neurohypophysial system.
  • It is this hypothalamic–neurohypophysial system which allowed the original formulation of the calcium hypothesis for stimulus–secretion coupling.
  • Arginine vasopressin is a vasoconstrictor and an antidiuretic and, thus, is involved in fluid homeostasis and osmoregulation.
  • Oxytocin has recognised functions in parturition and lactation and has an emerging role as a natriuretic agent.
  • Both hormones may also be central neurotransmitters and have been implicated in stress, learning and memory processes, social behaviours, as well as the development and maintenance of tolerance to ethanol and other drugs of abuse.
  • Oxytocin has possible therapeutic applications for social disorders such as autism.

Keywords: vasopressin; oxytocin; hypothalamus; neurohypophysis; posterior pituitary; osmoregulation; lactation

Figure 1. Anatomy of Magnocellular neurons. Schematic drawing of Magnocellular neurons (largest cells in pink) in the hypothalamic supraoptic nucleus and paraventricular nucleus projecting via hypothalamic and hypophyseal tracts to the neurohypophysis and adenohypophysis, the latter arising mainly from Parvocellular neurons in the paraventricular nucleus. Note axons projecting to other CNS targets and afferent projections from osmoreceptors in the subfornical organ and the organum vasculosum of the lamina terminalis.
Figure 2. Model of stimulus–secretion coupling at neurohypophysial terminals. Action potentials invading the terminal lead to its depolarization and the opening of voltage‐dependent calcium channels. These channels are differentially distributed in the hypothalamic–neurohypophysial system terminals: the (L) type are found diffusely throughout, while the (N) type appears to be co‐localised with release sites in both types of terminal. The (Q) type appears to be found only in arginine vasopressin (AVP)‐releasing hypothalamic–neurohypophysial system terminals, while the (R)‐type is only on oxytocin‐releasing hypothalamic–neurohypophysial system terminals (not shown). Intracellular Ca2+ release from ryanodine receptor (RyR) channels could also contribute to intracellular Ca2+[Ca]. Co‐released adenosine triphosphate (ATP) can act via P2X receptors to increase [Ca] and subsequent arginine vasopressin release. After its breakdown by ectoATPases, adenosine inhibits release via the A1 receptor's membrane‐delimited pathway (shown by arrow). DynA, an endogenous opioid, co‐release is another of many examples of such autoregulation in the hypothalamic–neurohypophysial system.
Figure 3. Model of hormonal feedback regulation of Magnocellular neurons. The hormones, oxytocin (OT) and arginine vasopressin (AVP), perhaps released locally from dendrites, increase Ca2+ levels in OT‐ and AVP‐synthesizing Magnocellular neurons, respectively. This autofeedback is mediated via specific receptors and involves different intracellular mechanisms. Although both types of Magnocellular neuron express T‐, L‐, N‐, P‐, Q‐ and R‐type Ca2+ channels, the arginine vasopressin response is mediated mainly by T, L and N types while voltage‐gated channels are not involved in the OT response. This response is via IP3‐mediated release of intracellular Ca2+. Courtesy of Dr. Govindan Dayanithi.
Figure 4. Regulation of HNS functions: Model of the two types (OT, oxytocinergic vs AVP, vasopressinergic) of Magnocellular neurons and the numerous agents (see also, Viero and Dayanithi, ) that modulate their function. These modulatory inputs (arrows) are localised to soma, dendrites, axon (burst patterns) and terminals of each type of Magnocellular neuron. Abbreviations: ACh, acetylcholine; ATP, adenosine triphosphate; ATP2×2, purinergic receptor 2x2; ATP2x7, purinergic receptor 2x7; AII, angiotensin II; AVP, arginine vasopressin; ANP, atrial natriuretic peptide; CCK, cholecystokinin; DA, dopamine; GABA, γ‐aminobutyric acid; EtOH, ethanol; His, histamine; MSH, Melanocyte‐stimulating hormone; NO, nitric oxide; NA, nor‐adrenaline; opioids: dynorphinA, DynA; & MetEnk, met‐enkephalin; OT, oxytocin; PGE2, prostaglandin E2; PACAP, pituitary adenylate cyclase‐activating polypeptide; 5HT, serotonin; SRIF, somatostatin release inhibiting factor; SP, substance P.
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References

Bourque CW, Oliet SHR and Richard D (1994) Osmoreceptors, osmoreception, and osmoregulation. Frontiers in Neuroendocrinology 15 (3): 231–274.

De Crescenzo V, ZhuGe R, Velázquez‐Marrero C, et al. (2004) Ca2+ syntillas, miniature Ca2+ release events in terminals of hypothalamic neurons, are increased in frequency by depolarization in the absence of Ca2+ influx. Journal of Neuroscience 24 (5): 1226–1235.

Douglas WW and Poisner AM (1964) Stimulus‐secretion coupling in a neurosecretory organ: the role of calcium in the release of vasopressin from the neurohypophysis. Journal of Physiology 172: 1–18.

Du Vigneaud V, Ressler C and Trippett S (1953) The sequence of amino acids in oxytocin, with a proposal for the structure of oxytocin. Journal of Biological Chemistry 205: 949–957.

Gainer H and Chin H (1998) Molecular diversity in neurosecretion: reflections on the hypothalamo‐neurohypophysial system. Cellular and Molecular Neurobiology 18 (2): 211–230.

Gross P, Richter D and Robertson GL (eds) (1993) Vasopressin: IVth International Conference. John Libbey Eurotex: Berlin.

Ivell R and Russell JA (eds) (1995) Oxytocin: Cellular and Molecular Approaches in Medicine and Research, vol. 395. Plenum Press: New York.

Jin D, Liu HX, Hirai H, et al. (2007) CD38 is critical for social behaviour by regulating oxytocin secretion. Nature 446: 41–45.

Lemos JR, Ortiz‐Miranda S, Cuadra A, et al. (2012) Modulation/physiology of calcium channel sub‐types in neurohypophysial terminals. Cell Calcium 51 (3–4): 284–292. DOI: 10.1016/j.ceca.2012.01.008.

Ludwig M, Sabatier N, Bull PM, et al. (2002) Intracellular calcium stores regulate activity‐dependent neuropeptide release from dendrites. Nature 418 (6893): 85–89.

Manning M, Stoev S, Chini B, et al. (2008) Peptide and non‐peptide agonists and antagonists for the vasopressin and oxytocin V1a, V1b, V2 and oxytocin receptors: research tools and potential therapeutic agents. Progress in Brain Research 170: 473–512.

Pietrzykowski AZ, Martin GE, Puig SI, et al. (2004) Alcohol tolerance in large‐conductance, calcium‐activated potassium channels of CNS terminals is intrinsic and includes two components: decreased ethanol potentiation and decreased channel density. Journal of Neuroscience 24 (38): 8322–8332.

Poulain DA and Wakerly JB (1982) Electrophysiology of hypothalamic magnocellular neurones secreting oxytocin and vasopressin. Neuroscience 7: 773–808.

Robertson GL (1985) Diagnosis of diabetes insipidus. In: Czernichow P and Robinson AG (eds) Frontiers of Hormone Research, pp 176–190. S. Karger: Basel.

Stopa EG, LeBlanc VK, Hill DH and Anthony EL (1993) A general overview of the anatomy of the neurohypophysis. Annals of the New York Academy of Sciences 689: 6–15.

Theodosis DT, El Majdoubi M, Pierre K and Poulain DA (1998) Factors governing activity‐dependent structural plasticity of the hypothalamoneurohypophysial system. Cellular and Molecular Neurobiology 18: 285–298.

Velazquez‐Marrero C, Custer EE, Ortiz‐Miranda S and Lemos JR (2020) Voltage‐induced Ca2+ release via ryanodine receptor causes neuropeptide secretion from CNS terminals. Journal of Neuroendocrinology, in press.

Viero C and Dayanithi G (2008) Neurosteroids are excitatory in supraoptic neurons but inhibitory in the peripheral nervous system: it is all about oxytocin and progesterone receptors. Progress in Brain Research 170: 177–192.

Nordmann JJ, Dayanithi G and Lemos JR (1987) Isolated neurosecretory nerve endings as a tool for studying the mechanism of stimulus‐secretion coupling. Bioscience Reports 7: 411–425.

Further Reading

Armstrong WE and Hatton GI (2006) The puzzle of pulsatile oxytocin secretion during lactation: some new pieces. American Journal of Physiology‐Regulatory, Integrative and Comparative Physiology 291 (1): R26–R28.

Bourque CW and Oliet SHR (1997) Osmoreceptors in the CNS. Annual Review of Physiology 59: 601–619.

Ludwig M and Leng G (2006) Dendritic peptide release and peptide‐dependent behaviours. Nature Reviews Neuroscience 7 (2): 126–136.

Ueta Y, Fujihara H, Dayanithi G, Kawata M and Murphy D (2008) Specific expression of optically active reporter gene in arginine vasopressin‐secreting neurosecretory cells in the hypothalamic‐neurohypophyseal system. Journal of Neuroendocrinology 20 (6): 660–664.

Veenema AH and Neumann ID (2008) Central vasopressin and oxytocin release: regulation of complex social behaviours. Progress in Brain Research 170: 261–276.

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Lemos, José R(Mar 2020) Magnocellular Neurons of the Hypothalamus. In: eLS. John Wiley & Sons Ltd, Chichester. http://www.els.net [doi: 10.1002/9780470015902.a0000176.pub3]