A career in numbers: A citation network analysis of the work of RP Millar and his contribution to GnRH research.

Here, we reflect on the long career in neuroendocrinology of a single, highly productive scientist ('Bob' Millar), by analysing his oeuvre of published papers through the lens of citation metrics. We use citation network analysis in a novel manner to identify the specific topics to which his papers have made a particular contribution, allowing us to compare the citations of his papers with those of contemporary papers on the same topic, rather than on the same broad field as generally used to normalise citations. It appears that citation rates are highest for topics on which Bob has published a relatively large number of papers that have become core to a tightly-knit community of authors that cite each other.

Measuring oxytocin release in response to gavage: Computational modelling and assay validation.

In the present experiments, we tested the conclusion from previous electrophysiological experiments that gavage of sweet food and systemically applied insulin both stimulate oxytocin secretion. To do so, we measured oxytocin secretion from urethane-anaesthetised male rats, and demonstrated a significant increase in secretion in response to gavage of sweetened condensed milk but not isocaloric cream, and a significant increase in response to intravenous injection of insulin. We compared the measurements made in response to sweetened condensed milk with the predictions from a computational model, which we used to predict plasma concentrations of oxytocin from the published electrophysiological responses of oxytocin cells.

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.

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.

Social touch promotes interfemale communication via activation of parvocellular oxytocin neurons.

Oxytocin (OT) is a great facilitator of social life but, although its effects on socially relevant brain regions have been extensively studied, OT neuron activity during actual social interactions remains unexplored. Most OT neurons are magnocellular neurons, which simultaneously project to the pituitary and forebrain regions involved in social behaviors. In the present study, we show that a much smaller population of OT neurons, parvocellular neurons that do not project to the pituitary but synapse onto magnocellular neurons, is preferentially activated by somatosensory stimuli.

Peripheral insulin administration enhances the electrical activity of oxytocin and vasopressin neurones in vivo.

Oxytocin neurones are involved in the regulation of energy balance through diverse central and peripheral actions and, in rats, they are potently activated by gavage of sweet substances. Here, we test the hypothesis that this activation is mediated by the central actions of insulin. We show that, in urethane-anaesthetised rats, oxytocin cells in the supraoptic nucleus show prolonged activation after i.

IGFBP2 Plays an Essential Role in Cognitive Development during Early Life.

Identifying the mechanisms underlying cognitive development in early life is a critical objective. The expression of insulin-like growth factor binding protein 2 (IGFBP2) in the hippocampus increases during neonatal development and is associated with learning and memory, but a causal connection has not been established. Here, it is reported that neurons and astrocytes expressing IGFBP2 are distributed throughout the hippocampus.

Coding of odors in the anterior olfactory nucleus.

Odorant molecules stimulate olfactory receptor neurons, and axons of these neurons project into the main olfactory bulb where they synapse onto mitral and tufted cells. These project to the primary olfactory cortex including the anterior olfactory nucleus (AON), the piriform cortex, amygdala, and the entorhinal cortex. The properties of mitral cells have been investigated extensively, but how odor information is processed in subsequent brain regions is less well known.

Effects of optogenetic stimulation of vasopressinergic retinal afferents on suprachiasmatic neurones.

Physiological circadian rhythms are orchestrated by the hypothalamic suprachiasmatic nucleus (SCN). The activity of SCN cells is synchronised by environmental signals, including light information from retinal ganglion cells (RGCs). We recently described a population of vasopressin-expressing RGCs (VP-RGC) that send axonal projections to the SCN.

Emergent decision-making behaviour and rhythm generation in a computational model of the ventromedial nucleus of the hypothalamus.

The ventromedial nucleus of the hypothalamus (VMN) has an important role in diverse behaviours. The common involvement in these of sex steroids, nutritionally-related signals, and emotional inputs from other brain areas, suggests that, at any given time, its output is in one of a discrete number of possible states corresponding to discrete motivational drives. Here we explored how networks of VMN neurons might generate such a decision-making architecture.

The vasopressin-memory hypothesis: a citation network analysis of a debate.

The 1970s saw a growing interest in the vasopressin-memory hypothesis, proposed by David de Wied and his collaborators in Utrecht. This rose to a peak in the 1980s that saw a flurry of papers published from diverse sources critical of the experimental foundations of this idea. In subsequent years, interest in this hypothesis declined markedly as shortcomings were recognized.

The spiking and secretory activity of oxytocin neurones in response to osmotic stimulation: a computational model.

Key Points: A quantitative model of oxytocin neurones that combines a spiking model, a model of stimulus-secretion coupling and a model of plasma clearance of oxytocin was tested. To test the model, a variety of sources of published data were used that relate either the electrical activity of oxytocin cells or the secretion of oxytocin to experimentally induced changes in plasma osmotic pressure. To use these data to test the model, the experimental challenges involved were computationally simulated.

The osmoresponsiveness of oxytocin and vasopressin neurones: Mechanisms, allostasis and evolution.

In the rat supraoptic nucleus, every oxytocin cell projects to the posterior pituitary, and is involved both in reflex milk ejection during lactation and in regulating uterine contractions during parturition. All are also osmosensitive, regulating natriuresis. All are also regulated by signals that control appetite, including the neural and hormonal signals that arise from the gut after food intake and from the sites of energy storage.

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.

Models in neuroendocrinology.

The neuroendocrine systems of the hypothalamus are critical for survival and reproduction, and are highly conserved throughout vertebrate evolution. Their roles in controlling body metabolism, growth and body composition, stress, electrolyte balance and reproduction have been intensively studied, and have yielded a rich crop of original and challenging insights into neuronal function, insights that circumscribe a vision of the brain that is quite different from conventional views. Despite the diverse physiological roles of pituitary hormones, most are secreted in a pulsatile pattern, but arising through a variety of mechanisms.

A Predictive, Quantitative Model of Spiking Activity and Stimulus-Secretion Coupling in Oxytocin Neurons.

Oxytocin neurons of the rat hypothalamus project to the posterior pituitary, where they secrete their products into the bloodstream. The pattern and quantity of that release depends on the afferent inputs to the neurons, on their intrinsic membrane properties, and on nonlinear interactions between spiking activity and exocytosis: A given number of spikes will trigger more secretion when they arrive close together. Here we present a quantitative computational model of oxytocin neurons that can replicate the results of a wide variety of published experiments.

Spike patterning in oxytocin neurons: Capturing physiological behaviour with Hodgkin-Huxley and integrate-and-fire models.

Integrate-and-fire (IF) models can provide close matches to the discharge activity of neurons, but do they oversimplify the biophysical properties of the neurons? A single compartment Hodgkin-Huxley (HH) model of the oxytocin neuron has previously been developed, incorporating biophysical measurements of channel properties obtained in vitro. A simpler modified integrate-and-fire model has also been developed, which can match well the characteristic spike patterning of oxytocin neurons as observed in vivo. Here, we extended the HH model to incorporate synaptic input, to enable us to compare spike activity in the model with experimental data obtained in vivo.

Vasopressin casts light on the suprachiasmatic nucleus.

Key Points: A subpopulation of retinal ganglion cells expresses the neuropeptide vasopressin. These retinal ganglion cells project predominately to our biological clock, the suprachiasmatic nucleus (SCN). Light-induced vasopressin release enhances the responses of SCN neurons to light.

Oxytocin - The Sweet Hormone?

Mammalian neurons that produce oxytocin and vasopressin apparently evolved from an ancient cell type with both sensory and neurosecretory properties that probably linked reproductive functions to energy status and feeding behavior. Oxytocin in modern mammals is an autocrine/paracrine regulator of cell function, a systemic hormone, a neuromodulator released from axon terminals within the brain, and a 'neurohormone' that acts at receptors distant from its site of release. In the periphery oxytocin is involved in electrolyte homeostasis, gastric motility, glucose homeostasis, adipogenesis, and osteogenesis, and within the brain it is involved in food reward, food choice, and satiety.

The determinants of food choice.

Health nudge interventions to steer people into healthier lifestyles are increasingly applied by governments worldwide, and it is natural to look to such approaches to improve health by altering what people choose to eat. However, to produce policy recommendations that are likely to be effective, we need to be able to make valid predictions about the consequences of proposed interventions, and for this, we need a better understanding of the determinants of food choice. These determinants include dietary components (e.

The rat suprachiasmatic nucleus: the master clock ticks at 30 Hz.

Key Points: Light-responsive neurones in the rat suprachiasmatic nucleus discharge with a harmonic distribution of interspike intervals, whereas unresponsive neurones seldom do. This harmonic patterning has a fundamental frequency of close to 30 Hz, and is the same in light-on cells as in light-off cells, and is unaffected by exposure to light. Light-on cells are more active than light-off cells in both subjective day and subjective night, and both light-on cells and light-off cells respond more strongly to changes in light intensity during the subjective night than during the subjective day.