α-Melanocyte-Stimulating Hormone Stimulates Oxytocin Release from the Dendrites of Hypothalamic Neurons While Inhibiting Oxytocin Release from Their Terminals in the Neurohypophysis

Sabatier, Nancy; Caquineau, Céline; Dayanithi, Govindan; Bull, Philip M.; Douglas, Alison J.; Guan, Xiaofei; Jiang, Michael; Ploeg, Lex Van der; Leng, Gareth

doi:10.1523/jneurosci.23-32-10351.2003

Cited by 192 publications

(182 citation statements)

References 44 publications

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“…Asynchronous release is not dependent on postsynaptic cell phenotype Oxytocin (OT) MNCs can release OT (Moos et al, 1989;Brussaard et al, 1996;Kombian et al, 1997;Ludwig et al, 2002;Sabatier et al, 2003) and endocannabinoids (Hirasawa et al, 2004;Oliet et al, 2007) from their dendrites. Likewise, vasopressin (VP) cells can release VP (Pow and Morris, 1989) or dynorphin (Watson et al, 1982).…”

Section: Prolonged Epsps In Mncs Results From Asynchronous Glutamate Rmentioning

confidence: 99%

Integration of Asynchronously Released Quanta Prolongs the Postsynaptic Spike Window

Iremonger¹,

Bains²

2007

Journal of Neuroscience

105

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Classically, the release of glutamate in response to a presynaptic action potential causes a brief increase in postsynaptic excitability. Previous reports indicate that at some central synapses, a single action potential can elicit multiple, asynchronous release events. This raises the possibility that the temporal dynamics of neurotransmitter release may determine the duration of altered postsynaptic excitability. In response to physiological challenges, the magnocellular neurosecretory cells (MNCs) in the paraventricular nucleus of the hypothalamus (PVN) exhibit robust and prolonged increases in neuronal activity. Although the postsynaptic conductances that may facilitate this form of activity have been investigated thoroughly, the role of presynaptic release has been largely overlooked. Because the specific patterns of activity generated by MNCs require the activation of excitatory synaptic inputs, we sought to characterize the release dynamics at these synapses and determine whether they contribute to prolonged excitability in these cells. We obtained whole-cell recordings from MNCs in brain slices of postnatal day 21-44 rats. Stimulation of glutamatergic inputs elicited large and prolonged postsynaptic events that resulted from the summation of multiple, asynchronously released quanta. Asynchronous release was selectively inhibited by the slow calcium buffer EGTA-AM and potentiated by brief high-frequency stimulus trains. These trains caused a prolonged increase in postsynaptic spike activity that could also be eliminated by EGTA-AM. Our results demonstrate that glutamatergic terminals in PVN exhibit asynchronous release, which is important in generating large postsynaptic depolarizations and prolonged spiking in response to brief, high-frequency bursts of presynaptic activity.

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Section: Prolonged Epsps In Mncs Results From Asynchronous Glutamate Rmentioning

confidence: 99%

Integration of Asynchronously Released Quanta Prolongs the Postsynaptic Spike Window

Iremonger¹,

Bains²

2007

Journal of Neuroscience

105

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“…A link between POMC and OT neurons in hypothalamus was provided by Sabatier and colleagues (29), and the obese phenotype of Sim-1-deficient mice has been hypothesized to be causally linked to the significant decreases of PVN OT and melanocortin 4 receptor mRNAs in those animals (14,37). CRH receptors are expressed in OT neurons in the PVN (1, 6).…”

Section: Discussionmentioning

confidence: 99%

Neural circuitry underlying the central hypertensive action of nesfatin-1: melanocortins, corticotropin-releasing hormone, and oxytocin

Yosten

Samson

2014

American Journal of Physiology-Regulatory, Integrative and Comp

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Yosten GL, Samson WK. Neural circuitry underlying the central hypertensive action of nesfatin-1: melanocortins, corticotropin-releasing hormone, and oxytocin. Am J Physiol Regul Integr Comp Physiol 306: R722-R727, 2014. First published March 5, 2014 doi:10.1152/ajpregu.00396.2013.-Nesfatin-1 is produced in the periphery and in the brain where it has been demonstrated to regulate appetite, stress hormone secretion, and cardiovascular function. The anorexigenic action of central nesfatin-1 requires recruitment of neurons producing the melanocortins and centrally projecting oxytocin (OT) and corticotropin-releasing hormone (CRH) neurons. We previously have shown that two components of this pathway, the central melanocortin and oxytocin systems, contribute to the hypertensive action of nesfatin-1 as well. We hypothesized that the cardiovascular effect of nesfatin-1 also was dependent on activation of neurons expressing CRH receptors, and that the order of activation of the melanocortin-CRH-oxytocin circuit was preserved for both the anorexigenic and hypertensive actions of the peptide. Pretreatment of male rats with the CRH-2 receptor antagonist astressin2B abrogated nesfatin-1-induced increases in mean arterial pressure (MAP). Furthermore, the hypertensive action of CRH was blocked by pretreatment with an oxytocin receptor antagonist ornithine vasotocin (OVT), indicating that the hypertensive effect of nesfatin-1 may require activation of oxytocinergic (OTergic) neurons in addition to recruitment of CRH neurons. Interestingly, we found that the hypertensive effect of ␣-melanocyte stimulating hormone (␣-MSH) itself was not blocked by either astressin2B or OVT. These data suggest that while ␣-MSH-producing neurons are part of a core melanocortin-CRHoxytocin circuit regulating food intake, and a subpopulation of melanocortin neurons activated by nesfatin-1 do mediate the hypertensive action of the peptide, ␣-MSH can signal independently from this circuit to increase MAP. nesfatin-1; melanocortin; central control of blood pressure; oxytocin; CRH HYPERTENSION, a major comorbidity of obesity, is present in over 50% of overweight and obese patients (19). While the etiology of obesity-associated hypertension is not fully understood, many obese patients exhibit an elevation in sympathetic nervous system (SNS) activity, as measured by microneurography (38) or elevated serum catecholamines (39). It is unclear whether the relationship between obesity and sympathoactivation is causal or correlative; however, several potential mechanisms have been proposed for their co-occurrence. One such hypothesis centers on the role of the adipocyte-derived hormone leptin, which acts centrally to inhibit food intake and increase SNS activity and subsequently mean arterial pressure (MAP). It has been suggested that in the setting of obesity, a state of leptin hypersecretion (32), individuals develop selective resistance to leptin, wherein they are incapable of responding to the anorexigenic effect of the peptide, yet continue to exhibit lep...

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“…Spike activity in oxytocin or vasopressin neurons in vivo does not result in measurable dendritic peptide release, but agents that mobilize Ca 2þ from intracellular stores, such as thapsigargin or cyclopiazonic acid, or some peptides, including oxytocin itself and a-MSH, consistently induce dendritic release directly [17,67]. It seems possible that any signal that mobilizes Ca 2þ from intracellular stores might prime dendritic secretion.…”

Section: (I) Calcium-dependent Priming Of Dendritic Releasementioning

confidence: 99%

“…For example, a dissociation between dendritic and axon terminal oxytocin release is evident from the effects of alpha melanocyte-stimulating hormone (a-MSH). Activation of melanocortin 4 receptors on oxytocin cells by a-MSH mobilizes intracellular calcium and stimulates dendritic oxytocin release, but the electrical activity of the cell is inhibited, leading to less oxytocin release into the periphery [17]. Another example of dissociated release patterns is that of vasopressin release into the periphery to counteract water-loss from the kidneys in response to increased plasma osmolality.…”

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confidence: 99%

Multiple signalling modalities mediated by dendritic exocytosis of oxytocin and vasopressin

Ludwig

Stern

2015

Phil. Trans. R. Soc. B

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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

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α-Melanocyte-Stimulating Hormone Stimulates Oxytocin Release from the Dendrites of Hypothalamic Neurons While Inhibiting Oxytocin Release from Their Terminals in the Neurohypophysis

Cited by 192 publications

References 44 publications

Integration of Asynchronously Released Quanta Prolongs the Postsynaptic Spike Window

Integration of Asynchronously Released Quanta Prolongs the Postsynaptic Spike Window

Neural circuitry underlying the central hypertensive action of nesfatin-1: melanocortins, corticotropin-releasing hormone, and oxytocin

Multiple signalling modalities mediated by dendritic exocytosis of oxytocin and vasopressin

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