Vasopressin and oxytocin release within the brain: a dynamic concept of multiple and variable modes of neuropeptide communication

doi:10.1016/j.yfrne.2004.05.001

Frontiers in Neuroendocrinology

Volume 25, Issues 3–4, September–December 2004, Pages 150-176

https://doi.org/10.1016/j.yfrne.2004.05.001 Get rights and content

Abstract

As exemplified particularly with vasopressin and oxytocin, release of neuropeptides within the brain occurs from dendrites, somata, and axons of neurosecretory neurons; mechanisms include activation of intracellular Ca²⁺ stores, changed strength of synaptic input and altered interaction between transcription factors and gene promoters. Upon demand, both diffuse spread of neuropeptides in the extracellular fluid following dendritic release and focal release from axonal terminals may contribute to regionally and temporally varying combinations of neuromodulator and neurotransmitter actions, thus providing a theoretically unlimited variability in interneuronal signaling. Thus, instead of favoring volume or synaptic transmission following central neuropeptide release, a more dynamic concept is presented with multiple and variable modes of release and communication. This concept considers neuropeptides in the extracellular fluid of the brain rather than those in the cerebrospinal fluid or plasma as primary signals, triggering a variety of receptor-mediated effects, including those underlying behavioral and neuroendocrine regulation and psychopathology.

Section snippets

Introduction: historical background of neuropeptide research

The roots of neuropeptide research may be traced back to the end of the 19th century, when G. Oliver and E.A. Schäfer in 1893 provided first evidence that the posterior pituitary gland does indeed have some function and Ramon y Cajal in 1894 described a neural pathway from the supraoptic nucleus (SON) of the hypothalamus to the posterior pituitary. In the 1930s, E. and B. Scharrer demonstrated that certain neurons in the hypothalamus of invertebrates as well as vertebrates secrete substances

Neuropeptides: synthesis and intracellular processing

Neuropeptides are biologically active sequences of three or more amino acid residues, which are produced in and released from distinct populations of neurons and are capable of influencing functional parameters of target neurons via G-protein-coupled receptors. Sensitive molecular–neuroanatomical techniques have confirmed that mRNAs and their encoded neuropeptides are found in virtually every type of neuron (and glial cell [239]), and in almost every region of the central nervous system (for

Technical approaches to monitor central neuropeptide release

Central release patterns finally determining the concentration of biologically active neuropeptides in the extracellular fluid (including that in the synaptic cleft) of a given brain area are crucial in the cascade of events from neuropeptide synthesis to receptor binding. However, while events including transcription, processing, and receptor distribution have well been described, the mechanisms, dynamics, and consequences of central release of many neuropeptides are largely unknown. In many

Multiple and variable modes of communication

Once released within the brain, the role of neuropeptides in interneuronal communication (including feed-back actions on their own neurons) is based on multiple actions as neuromodulators and/or neurotransmitters; additionally, secreted into the systemic circulation, neuropeptides may act as hormones. As transmitters, neuropeptides contribute to the synaptic mode of information transfer, which refers to fast point-to-point signaling including transient actions, which are limited to

Stimuli and mechanisms of central release of oxytocin and vasopressin

As mentioned before, OXT and AVP neurons in the hypothalamic SON and PVN have served as important models of neuropeptide release within the brain. These two neuronal phenotypes show overlapping but distinct gene expression and secretion patterns into the systemic circulation. Compared to the latter, which is excellently described, little is known about the stimuli and mechanisms of dendritic release, but it is nevertheless likely that this limited information will serve as a model for central

Functional consequences of central release of vasopressin and oxytocin

As has been discussed in Section 4.1, neuropeptide actions can simultaneously include regionally and temporally varying combinations of neurotransmitter and neuromodulator activities. These combined activities are likely to reach a high level of regulatory capacity, synergistically including all advantages from precise point-to-point signaling up to diffusely spread neuromodulation, thereby liberating the brain from the constraints of wiring. According to our concept, this regulatory capacity

Central release of other neuropeptides

In addition to AVP and OXT, other neuropeptides including CRF [85], [168], [171], [172], [226], substance P [62], [289], and prolactin [261] have been shown to be released within the brain (Table 2). In most cases, however, mechanisms and modes of release are largely unknown. Therefore, it remains to be shown, whether these neuropeptides add further support to the dynamic concept of multiple and variable modes of interneuronal communication, as discussed in this review.

Conclusion

Compared to peripheral secretion into systemic circulation, little is known about central release patterns of neuropeptides, including stimuli, mechanisms, and consequences. Generally, findings based on measurements in plasma and CSF are not a reliable guide to neuropeptide changes in the extracellular fluid of distinct brain areas. Similarly, in situ hybridization and receptor autoradiography, often used as indices of activity of a neuropeptidergic system, are not closely linked to release of

Acknowledgements

We thank our colleagues and friends DRS. M. Engelmann, M. Ludwig, N. Singewald, and C.T. Wotjak for advice and collaboration.

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Vasopressin and oxytocin release within the brain: a dynamic concept of multiple and variable modes of neuropeptide communication

Abstract

Section snippets

Introduction: historical background of neuropeptide research

Neuropeptides: synthesis and intracellular processing

Technical approaches to monitor central neuropeptide release

Multiple and variable modes of communication

Stimuli and mechanisms of central release of oxytocin and vasopressin

Functional consequences of central release of vasopressin and oxytocin

Central release of other neuropeptides

Conclusion

Acknowledgements

Neurosci. Biobehav. Rev

Neurochem. Int

Life Sci

Exp. Neurol

Prog. Neurobiol

Neuroscience

Trends Neurosci

Eur. J. Pharmacol

Neurosci. Res

Trends Neurosci

Neuron

Front. Neuroendocrinol

J. Biol. Chem

Neuroscience

Brain Res. Bull

Brain Res

J. Neurosci. Methods

Brain Res

Physiol. Behav

Neurosci. Lett

Peptides

Neurosci. Lett

Brain Res

Brain Res. Bull

Front. Neuroendocrinol

Brain Res

Physiol. Behav

Brain Res

Neurosci. Biobehav. Rev

Prog. Neurobiol

Front. Neuroendocrinol

Neurosci. Lett

Prog. Brain Res

Brain Res

Prog. Neurobiol

Brain Res

Brain Res. Bull

Prog. Neurobiol

Volume versus wiring transmission in the brain: a new theoretical frame for neuropsychopharmacology

Med. Res. Rev

The role of corticotropin-releasing factor in depression and anxiety disorders

J. Endocrinol

Sorting and storage during secretory granules biogenesis: looking backward and looking forward

Biochem. J

CNS region-specific oxytocin receptor expression: importance in regulation of anxiety and sex behaviour

J. Neurosci

GABAergic control of neuropeptide gene expression in parvocellular neurons of the hypothalamic paraventricular nucleus

Eur. J. Neurosci

Vasopressin and oxytocin receptors in the central nervous system

Crit. Rev. Neurobiol

Stimulation of central and systemic oxytocin release by histamine in the paraventricular hypothalamic nucleus: evidence for an interaction with norepinephrine

Endocrinology

Do centrally administered neuropeptides access cognate receptors? An analysis in the central corticotropin-releasing factor system

J. Neurosci

Changes in oxytocin immunoreactivity and mRNA expression in the sheep brain during pregnancy, parturition and lactation and in response to oestrogen and progesterone

J. Neuroendocrinol

Oxytocin neurone autoexcitation during morphine withdrawal in anaesthetized rats

Neuroreport

Postsynaptic mechanism of depression of GABAergic synapses by oxytocin in the supraoptic nucleus of immature rat

J. Physiol