Centre for Discovery Brain Sciences, University of Edinburgh, Hugh Robson Building, George Square, Edinburgh EH8 9XD, UK.
Math Biosci. 2018 Nov;305:29-41. doi: 10.1016/j.mbs.2018.07.008. Epub 2018 Aug 1.
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. An important exception is vasopressin which uses bursting neural activity, but produces a graded secretion response to osmotic pressure, a sustained robust linear response constructed from noisy, nonlinear components. Neuroendocrine systems have many features such as multiple temporal scales and nonlinearity that make their underlying mechanisms hard to understand without mathematical modelling. The models presented here cover the wide range of temporal scales involved in these systems, including models of single cell electrical activity and calcium dynamics, receptor signalling, gene expression, coordinated activity of neuronal networks, whole-organism hormone dynamics and feedback loops, and the menstrual cycle. Many interesting theoretical approaches have been applied to these systems, but important problems remain, at the core the question of what is the true advantage of pulsatility.
下丘脑的神经内分泌系统对于生存和繁殖至关重要,并且在整个脊椎动物进化中高度保守。它们在控制身体代谢、生长和身体成分、应激、电解质平衡和生殖方面的作用已经得到了深入研究,为神经元功能提供了丰富的原创性和挑战性的见解,这些见解勾勒出了与传统观点截然不同的大脑图景。尽管垂体激素具有多种生理作用,但大多数激素都是以脉冲模式分泌的,但产生脉冲的机制却多种多样。一个重要的例外是血管加压素,它利用爆发性的神经活动,但对渗透压产生分级分泌反应,对持续的、稳健的线性反应进行构建,这个反应由嘈杂的非线性成分组成。神经内分泌系统具有许多特征,如多个时间尺度和非线性,这些特征使得如果没有数学建模,就很难理解其潜在机制。这里提出的模型涵盖了这些系统所涉及的广泛时间尺度,包括单个细胞电活动和钙动力学、受体信号转导、基因表达、神经元网络的协调活动、整个生物体的激素动力学和反馈回路以及月经周期的模型。许多有趣的理论方法已经应用于这些系统,但仍存在重要问题,核心问题是脉冲性的真正优势是什么。