Functional analysis of prolactin-sensitive neural circuits in the arcuate nucleus.

弓状核催乳素敏感神经回路的功能分析。

• 批准号: 406648336
• 负责人: Professor Dr. Ulrich Boehm
• 金额: --
• 依托单位: FR Experimentelle und Klinische Pharmakologie und Toxikologie
• 依托单位国家: 德国
• 项目类别: Research Grants
• 财政年份: 2018
• 资助国家: 德国
• 起止时间: 2017-12-31 至 2022-12-31
• 项目状态: 已结题
• 来源: https://gepris.dfg.de/gepris/projekt/406648336?language=en
• 关键词: Functional; analysis; prolactin; sensitive; neural

One of the great challenges remaining in integrative physiology today is to understand how the brain decodes fluctuating hormone levels to orchestrate precise and coordinated control over complex multifaceted physiological processes such as reproduction, lactation and metabolism. The hormone prolactin influences a wide range of physiological functions helping the mother adapt to the physiological demands of pregnancy and subsequent lactation. However, the neural circuits and individual neurons mediating prolactin actions in the brain are not well understood. PRL secretion by lactotrope cells in the anterior pituitary gland is thought to be primarily regulated by a single brain output signal, i.e. dopamine (DA), released by tuberoinfundibular dopaminergic (TIDA) neurons in the hypothalamic arcuate nucleus (ARC) and exerting an inhibitory tone on spontaneous PRL secretion. This seemingly simple regulation of PRL secretion is in stark contrast to the pleiotropic actions of PRL influencing an extremely wide range of functions (more than 300 described outputs so far!). Recent experimental evidence suggests that PRL functions may be controlled by specialized subsets of PRL-sensitive neurons within the ARC. This area of the hypothalamus is poised to serve as a prime target for PRL action since it contains a large number of PRL-sensitive neurons which have fast access to circulating PRL levels via fenestrated capillaries. The neuronal diversity of the ARC makes it a prime candidate to explain the diversity of PRL actions. Based on these hypotheses, our DFG-ANR consortium will investigate how specialized neural circuits in the hypothalamus decode fluctuating hormone levels and translate those into appropriate physiological and behavioral responses. The specific aim of the present study is to dissect and functionally analyze prolactin-sensitive neural circuits in the hypothalamic arcuate nucleus. To do this, we will capitalize on recently developed animal models giving us genetic access to these cells. We will explore this endocrine-brain dialog in male versus virgin and lactating female mice to address the long-standing question of how brain circuits adapt to the physiological demands during lactation.

当今综合生理学面临的最大挑战之一是了解大脑如何解码波动的激素水平，以协调精确和协调地控制复杂的多方面生理过程，如生殖，哺乳和代谢。催乳激素影响广泛的生理功能，帮助母亲适应怀孕和随后哺乳的生理需求。然而，神经回路和个别神经元介导的催乳素行动在大脑中没有很好地理解。垂体前叶催乳素细胞分泌PRL被认为主要受单一脑输出信号调节，即多巴胺（DA），其由下丘脑弓状核（ARC）中的结节漏斗多巴胺能（TIDA）神经元释放并对自发性PRL分泌施加抑制性张力。PRL分泌的这种看似简单的调节与PRL的多效性作用形成鲜明对比，PRL影响极其广泛的功能（迄今为止已描述了300多种输出！）。最近的实验证据表明，PRL功能可能是由ARC内的PRL敏感神经元的专门子集控制的。下丘脑的这个区域准备作为PRL作用的主要靶点，因为它含有大量PRL敏感神经元，这些神经元通过有孔毛细血管快速进入循环PRL水平。ARC的神经元多样性使其成为解释PRL作用多样性的主要候选者。基于这些假设，我们的DFG-ANR联盟将研究下丘脑中的专门神经回路如何解码波动的激素水平，并将其转化为适当的生理和行为反应。本研究的具体目的是解剖和功能分析催乳素敏感的神经回路在下丘脑弓状核。为了做到这一点，我们将利用最近开发的动物模型，使我们能够从基因上获得这些细胞。我们将在雄性与处女和哺乳期雌性小鼠中探索这种内分泌-大脑对话，以解决长期存在的问题，即大脑回路如何适应哺乳期的生理需求。