An intrinsic vasopressin system in the olfactory bulb is involved in social recognition.

Many peptides, when released as chemical messengers within the brain, have powerful influences on complex behaviours. Most strikingly, vasopressin and oxytocin, once thought of as circulating hormones whose actions were confined to peripheral organs, are now known to be released in the brain, where they have fundamentally important roles in social behaviours. In humans, disruptions of these peptide systems have been linked to several neurobehavioural disorders, including Prader-Willi syndrome, affective disorders and obsessive-compulsive disorder, and polymorphisms of V1a vasopressin receptor have been linked to autism. Here we report that the rat olfactory bulb contains a large population of interneurons which express vasopressin, that blocking the actions of vasopressin in the olfactory bulb impairs the social recognition abilities of rats and that vasopressin agonists and antagonists can modulate the processing of information by olfactory bulb neurons. The findings indicate that social information is processed in part by a vasopressin system intrinsic to the olfactory system.

Oxytocin and appetite.

Oxytocin has potent central effects on feeding behaviour, as well as on social and sexual behaviours, and one likely substrate for its anorectic effect is the ventromedial nucleus of the hypothalamus. This nucleus expresses a high density of oxytocin receptors, but contains very few oxytocin-containing fibres, hence it is a likely target of 'neurohormonal' actions of oxytocin, including possibly oxytocin released from the dendrites of magnocellular oxytocin neurones. As oxytocin release from dendrites is regulated independent of electrical activity and of secretion from the neurohypophysis, exactly how this release is regulated by metabolic and reproduction-related signals remains to be established fully. Intriguingly though, it looks as though this central release of oxytocin from magnocellular neurons might be instrumental in a fundamental shift in motivational behaviour - switching behaviour from being driven by the need to find and consume food, to the need to reproduce.

Priming in oxytocin cells and in gonadotrophs.

At proestrous, the sensitivity of gonadotrophs to gonadotrophin-releasing hormone (GnRH) increases with repeated exposure to GnRH, a process known as self-priming. An apparently similar phenomenon can also occur in peptidergic neurons; activity-dependent oxytocin release from dendrites can be potentiated by oxytocin itself. In the brain, such priming actions have the potential to alter the strength of communication between neuronal populations for a very prolonged period. In the case of both oxytocin neurons and gonadotrophs, priming appears to involve an augmentation of a readily releasable pool of vesicles.

Regulation of oxytocin secretion.

A baby sucks at a mother's breast for comfort and, of course, for milk. Milk is made in specialized cells of the mammary gland, and for a baby to feed, the milk must be released into a collecting chamber from where it can be extracted by sucking. Milk "let-down" is a reflex response to the suckling and kneading of the nipple--and sometimes in response to the sight, smell, and sound of the baby--and is ultimately affected by the secretion of oxytocin. Oxytocin has many physiological roles, but its only irreplaceable role is to mediate milk let-down: oxytocin-deficient mice cannot feed their young; the pups suckle but no milk is let down, and they will die unless cross-fostered. Most other physiological roles of oxytocin, including its role in parturition, are redundant in the sense that the roles can be assumed by other mechanisms in the absence of oxytocin throughout development and adult life. Nevertheless, physiological function in these roles can be altered or impaired by acute interventions that alter oxytocin secretion or change the actions of oxytocin. Here we focus on the diverse stimuli that regulate oxytocin secretion and on the apparent diversity of the roles for oxytocin.

Alpha-melanocyte-stimulating hormone stimulates oxytocin release from the dendrites of hypothalamic neurons while inhibiting oxytocin release from their terminals in the neurohypophysis.

The peptides alpha-melanocyte stimulating hormone (alpha-MSH) and oxytocin, when administered centrally, produce similar behavioral effects. alpha-MSH induces Fos expression in supraoptic oxytocin neurons, and alpha-MSH melanocortin-4 receptors (MC4Rs) are highly expressed in the supraoptic nucleus, suggesting that alpha-MSH and oxytocin actions are not independent. Here we investigated the effects of alpha-MSH on the activity of supraoptic neurons. We confirmed that alpha-MSH induces Fos expression in the supraoptic nucleus when injected centrally and demonstrated that alpha-MSH also stimulates Fos expression in the nucleus when applied locally by retrodialysis. Thus alpha-MSH-induced Fos expression is not associated with electrophysiological excitation of supraoptic neurons because central injection of alpha-MSH or selective MC4 receptor agonists inhibited the electrical activity of oxytocin neurons in the supraoptic nucleus recorded in vivo. Consistent with these observations, oxytocin secretion into the bloodstream decreased after central injection of alpha-MSH. However, MC4R ligands induced substantial release of oxytocin from dendrites in isolated supraoptic nuclei. Because dendritic oxytocin release can be triggered by changes in [Ca2+]i, we measured [Ca2+]i responses in isolated supraoptic neurons and found that MC4R ligands induce a transient [Ca2+]i increase in oxytocin neurons. This response was still observed in low extracellular Ca2+ concentration and probably reflects mobilization of [Ca2+]i from intracellular stores rather than entry via voltage-gated channels. Taken together, these results show for the first time that a peptide, here alpha-MSH, can induce differential regulation of dendritic release and systemic secretion of oxytocin, accompanied by dissociation of Fos expression and electrical activity.

Oxytocin released from magnocellular dendrites: a potential modulator of alpha-melanocyte-stimulating hormone behavioral actions?

Alpha-melanocyte-stimulating hormone (alpha-MSH) is implicated in a variety of behavioral processes that are remarkably similar to those behaviors in which centrally acting oxytocin has been implicated. Central oxytocin derives in part from centrally projecting parvocellular neurons of the paraventricular nucleus, but large amounts of oxytocin are also released from dendrites of magnocellular oxytocin neurons in the supraoptic and paraventricular nuclei of the hypothalamus. Oxytocin release from dendrites is semi-independent of electrical activity and can be modulated by peptidergic signals independently of release from nerve terminals. Oxytocin is released from dendrites by stimuli that mobilize intracellular calcium stores, and such stimuli also prime dendritic stores of oxytocin, making them available for subsequent activity-dependent secretion. Evidence exists for efferent projections to the supraoptic nucleus from the arcuate nucleus where alpha-MSH neurons are located, and the supraoptic and paraventricular nuclei show high levels of expression of mRNA for the melanocortin receptor MC4R. These projections may be involved specifically in the regulation of dendritic oxytocin release.