Multiple signalling modalities mediated by dendritic exocytosis of oxytocin and vasopressin

Abstract

The mammalian hypothalamic magnocellular neurons of the supraoptic and paraventricular nuclei are among the best understood of all peptidergic neurons. Through their anatomical features, vasopressin-and oxytocincontaining neurons have revealed many important aspects of dendritic functions. Here, we review our understanding of the mechanisms of somato-dendritic peptide release, and the effects of autocrine, paracrine and hormone-like signalling on neuronal networks and behaviour. Of secret messages and public announcementsForms of information processing and intercellular communication in the brain may be classified, at least in part, according to distinct spatio-temporal features. At one end of the spectrum is classical chemical synaptic transmission. Chemical synapses are structurally organized units with a well-defined physical substrate and have evolved to transfer information between pairs of neurons efficiently, in a precise, spatially constrained and rapid manner. The strength and time course of this 'hard-wired' communication is dependent on the probability of presynaptic transmitter release, the affinity of the postsynaptic receptors for the transmitter, the density of postsynaptic receptors clustered at highly specialized sites, and the rate of diffusion/uptake of the neurotransmitter at/from the synaptic cleft [1][2][3][4].At the opposite end of the spatio-temporal spectrum, paracrine or hormonelike signalling modalities mediate transfer of information between entire populations of neurons, which in some cases may be located relatively distant from each other, acting in a more diffuse, less spatially constrained manner and on a slower time scale. In the hard-wired chemical synapse, the 'secrecy' of the communication is largely determined by the spatially constrained structure of the synapse. Conversely, in paracrine transmission, specificity is solely determined by the specificity of the signal -receptor interaction. Examples of signalling mechanisms acting at more distant sites include release of catecholamines and acetylcholine from en passant boutons on axonal segments [5], and gaseous neurotransmitters, including nitric oxide and carbon monoxide [6]. However, the prototypes for hormone-like signalling within the brain are many neuropeptides, including vasopressin and oxytocin, released from their somata and dendrites. They are public announcements; they are messages not from one cell to another, but rather a message that is directed from one population of neurons to another [7][8][9].2. The hypothalamo-neurohypophysial axis: a model system to study dendritic peptide releaseThe dendrites of magnocellular neurons (MCNs) of the hypothalamic supraoptic nucleus (SON) and paraventricular nucleus (PVN) have some unique characteristics compared with other neurons in the central nervous system. They are aspiny, branch sparsely, in many cases are aggregated in bundles, and are

Release of chemical transmitters from cell bodies and dendrites of nerve cells

“…As with serotonin, the activity requirements for somatodendritic release of the neuropeptides vasopressin and oxytocin are distinct from those for release by nerve terminals [31]. Thus, as expected, large electrondense vesicles in axonal terminals of the magnocellular neurons of the hypothalamic supraoptic nucleus and paraventricular nucleus fuse with high reliability following individual action potentials.…”

Diversity of Axonal and Dendritic Contributions to Neuronal Output

“…Dopamine, glutamate, and GABA are not the only neurotransmitters to be released from dendrites. Dendritic release of the neuropeptides oxytocin and vasopressin by the magnocellular neurons of the supraoptic and paraventricular nuclei has been shown to play a critical role in the regulation of activity of this neuronal population (Ludwig et al, 2002; for review, see Ludwig and Leng, 2006;Ludwig and Stern, 2015;Ludwig et al, 2017). Somata and dendrites of these neurons have been shown to contain large amounts of neurosecretory granules (Pow and Morris, 1989) and SD release is induced by Ca 2+ increase (Ludwig et al, 2002).…”

Vasopressin at Central Levels and Consequences of Dehydration

“…Parvocellular pre-autonomic neurons of PVN send long descending projections to sympathetic and parasympathetic centers in the brain stem and spinal cord, modulating sympathetic and parasympathetic outflows to a variety of target organs, including the heart, the peripheral vasculature and the kidneys. In addition to neurosecretory and autonomic targets, PVNs also include neurons that project to higher centers in the brain, including the central amygdala, projections recently shown to modulate fearconditioned responses [13] . PVN also receive afferents from the nucleus solitarius and other spinal cardiovascular regulatory afferents, thereby coordinating sympathetic, parasympathetic and somatomotor information to the endocrine activity.…”

“…Axons and axonal collaterals project not only to the PP but also to the forebrain and limbic areas [2] . Dendritic release of VP, of considerable importance during dehydration to induce a central pre-autonomic stimulation [7] , leads to extremely high local brain concentrations of VP [12,13] . Parvocellular pre-autonomic neurons of PVN send long descending projections to sympathetic and parasympathetic centers in the brain stem and spinal cord, modulating sympathetic and parasympathetic outflows to a variety of target organs, including the heart, the peripheral vasculature and the kidneys.…”