Here, we construct a mathematical model of the hypothalamic systems that control the secretion of growth hormone (GH). The work extends a recent model of the pituitary GH system, adding representations of the hypothalamic GH-releasing hormone (GHRH) and somatostatin neurones, each modelled as a single synchronised unit. An unpatterned stochastic input drives the GHRH neurones generating pulses of GHRH release that trigger GH pulses. Delayed feedback from GH results in increased somatostatin release, which inhibits both GH secretion and GHRH release, producing an overall pattern of 3-h pulses of GH secretion that is very similar to the secretory profile observed in male rats. Rather than directly stimulating somatostatin release, GH feedback triggers a priming effect, increasing releasable stores of somatostatin. Varying this priming effect to reduce the effect of GH can reproduce the less pulsatile form of GH release observed in the female rat. The model behaviour is tested by comparison with experimental observations with a range of different experimental protocols involving GHRH injections and somatostatin and GH infusion.
"Development and testing of the model is in custom software built in C++ and wxWidgets, based on modelling and data analysis software we have previously developed to study diverse neuroendocrine systems (MacGregor and Leng, 2005; Macgregor and Lincoln, 2008; MacGregor et al., 2009). "
[Show abstract][Hide abstract] ABSTRACT: The task of the vasopressin system is homeostasis, a type of process which is fundamental to the brain's regulation of the body, exists in many different systems, and is vital to health and survival. Many illnesses are related to the dysfunction of homeostatic systems, including high blood pressure, obesity and diabetes. Beyond the vasopressin system's own importance, in regulating osmotic pressure, it presents an accessible model where we can learn how the features of homeostatic systems generally relate to their function, and potentially develop treatments. The vasopressin system is an important model system in neuroscience because it presents an accessible system in which to investigate the function and importance of, for example, dendritic release and burst firing, both of which are found in many systems of the brain. We have only recently begun to understand the contribution of dendritic release to neuronal function and information processing. Burst firing has most commonly been associated with rhythm generation; in this system it clearly plays a different role, still to be understood fully.
Bio Systems 03/2013; 112(2). DOI:10.1016/j.biosystems.2013.03.010 · 1.55 Impact Factor
"Besides the oxytocin model reviewed above, there are mathematical models of the pulsatile secretion of LHRH (Gordan et al., 1998; Scullion et al., 2004; Khadra and Li, 2006), the hypothalamic control of growth hormone secretion (MacGregor and Leng, 2005), and the bursting properties of vasopressin (Roper et al., 2004), etc. The recent model for LHRH revealed that LHRH plays the roles of feedback regulator and a diffusive synchronization effects in pulsatile secretion of LHRH from hypothalamic neurons. "
[Show abstract][Hide abstract] ABSTRACT: Classically, information processing in the brain involves fast signaling mechanisms at a vast number of discrete sites, via spike-dependent neurotransmitter release at synapses. However, neurons also use a huge diversity of slower analog signaling mechanisms, these chemical signaling pathways, acting in a more global spatial scale and on a longer temporal scale, are closely related to social behaviors and emotion. How do these parallel signaling systems interact to give rise to coherent behavioral consequences? In this review, we consider the role of the neuropeptide oxytocin in the milk-ejection reflex as an example of how a complex neural network involving a peptidergic signaling pathway underlies the complex physiological behavior.
Journal of Biotechnology 09/2010; 149(3):215-25. DOI:10.1016/j.jbiotec.2010.01.003 · 2.87 Impact Factor
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