The involvement of actin, calcium channels and exocytosis proteins in somato-dendritic oxytocin and vasopressin release

Hypothalamic magnocellular neurons release vasopressin and oxytocin not only from their axon terminals into the blood, but also from their somata and dendrites into the extracellular space of the brain, and this can be regulated independently. Differential release of neurotransmitters from different compartments of a single neuron requires subtle regulatory mechanisms. Somato-dendritic, but not axon terminal release can be modulated by changes in intracellular calcium concentration [(Ca(2+))] by release of calcium from intracellular stores, resulting in priming of dendritic pools for activity-dependent release. This review focuses on our current understanding of the mechanisms of priming and the roles of actin remodeling, voltage-operated calcium channels (VOCCs) and SNARE proteins in the regulation somato-dendritic and axon terminal peptide release

The Endocrinology of the Brain

The brain hosts a vast and diverse repertoire of neuropeptides, a class of signalling molecules often described as neurotransmitters. Here I argue that this description entails a catalogue of misperceptions, misperceptions that feed into a narrative in which information processing in the brain can be understood only through mapping neuronal connectivity and by studying the transmission of electrically conducted signals through chemical synapses. I argue that neuropeptide signalling in the brain involves primarily autocrine, paracrine and neurohormonal mechanisms that do not depend on synaptic connectivity and that it is not solely dependent on electrical activity but on mechanisms analogous to secretion from classical endocrine cells. As in classical endocrine systems, to understand the role of neuropeptides in the brain, we must understand not only how their release is regulated, but also how their synthesis is regulated and how the sensitivity of their targets is regulated. We must also understand the full diversity of effects of neuropeptides on those targets, including their effects on gene expression

Oxytocin:A citation network analysis of 10 000 papers

Our understanding of the oxytocin system has been built over the last 70 years by the work of hundreds of scientists, reported in thousands of papers. Here, we construct a map to that literature, using citation network analysis in conjunction with bibliometrics. The map identifies ten major ‘clusters’ of papers on oxytocin that differ in their particular research focus and that densely cite papers from the same cluster. We identify highly cited papers within each cluster and in each decade, not because citations are a good indicator of quality, but as a guide to recognising what questions were of wide interest at particular times. The clusters differ in their temporal profiles and bibliometric features; here, we attempt to understand the origins of these differences

Oxytocin—a social peptide? Deconstructing the evidence

In this paper, we analyse the claim that oxytocin is a ‘social neuropeptide’. This claim originated from evidence that oxytocin was instrumental in the initiation of maternal behaviour and it was extended to become the claim that oxytocin has a key role in promoting social interactions between individuals. We begin by considering the structure of the scientific literature on this topic, identifying closely interconnected clusters of papers on particular themes. We then analyse this claim by considering evidence of four types as generated by these clusters: (i) mechanistic studies in animal models, designed to understand the pathways involved in the behavioural effects of centrally administered oxytocin; (ii) evidence from observational studies indicating an association between oxytocin signalling pathways and social behaviour; (iii) evidence from intervention studies, mainly involving intranasal oxytocin administration; and (iv) evidence from translational studies of patients with disorders of social behaviour. We then critically analyse the most highly cited papers in each segment of the evidence; we conclude that, if these represent the best evidence, then the evidence for the claim is weak. This article is part of the theme issue ‘Interplays between oxytocin and other neuromodulators in shaping complex social behaviours’

Oxytocin, feeding, and satiety

Oxytocin neurones have a physiological role in food intake and energy balance. Central administration of oxytocin is powerfully anorexigenic, reducing food intake and meal duration. The central mechanisms underlying this effect of oxytocin have become better understood in the past few years. Parvocellular neurones of the paraventricular nucleus project to the caudal brainstem to regulate feeding via autonomic functions including the gastrointestinal vago-vagal reflex. In contrast, magnocellular neurones of the supraoptic and paraventricular nuclei release oxytocin from their dendrites to diffuse to distant hypothalamic targets involved in satiety.The ventromedial hypothalamus, for example, expresses a high density of oxytocin receptors but does not contain detectable oxytocin nerve fibres. Magnocellular neurones represent targets for the anorexigenic neuropeptide α-melanocyte stimulating hormone. . In addition to homeostatic control, oxytocin may also have a role in reward-related feeding. Evidence suggests that oxytocin can selectively suppress sugar intake and that it may have a role in limiting the intake of palatable food by inhibiting the reward pathway

Phasic Firing in Vasopressin Cells: Understanding Its Functional Significance through Computational Models

Vasopressin neurons, responding to input generated by osmotic pressure, use an intrinsic mechanism to shift from slow irregular firing to a distinct phasic pattern, consisting of long bursts and silences lasting tens of seconds. With increased input, bursts lengthen, eventually shifting to continuous firing. The phasic activity remains asynchronous across the cells and is not reflected in the population output signal. Here we have used a computational vasopressin neuron model to investigate the functional significance of the phasic firing pattern. We generated a concise model of the synaptic input driven spike firing mechanism that gives a close quantitative match to vasopressin neuron spike activity recorded in vivo, tested against endogenous activity and experimental interventions. The integrate-and-fire based model provides a simple physiological explanation of the phasic firing mechanism involving an activity-dependent slow depolarising afterpotential (DAP) generated by a calcium-inactivated potassium leak current. This is modulated by the slower, opposing, action of activity-dependent dendritic dynorphin release, which inactivates the DAP, the opposing effects generating successive periods of bursting and silence. Model cells are not spontaneously active, but fire when perturbed by random perturbations mimicking synaptic input. We constructed one population of such phasic neurons, and another population of similar cells but which lacked the ability to fire phasically. We then studied how these two populations differed in the way that they encoded changes in afferent inputs. By comparison with the non-phasic population, the phasic population responds linearly to increases in tonic synaptic input. Non-phasic cells respond to transient elevations in synaptic input in a way that strongly depends on background activity levels, phasic cells in a way that is independent of background levels, and show a similar strong linearization of the response. These findings show large differences in information coding between the populations, and apparent functional advantages of asynchronous phasic firing