前胰高血糖素原神经元及下丘脑向孤束核投射对应激相关行为的调节作用。
Modulation of stress-related behaviour by preproglucagon neurons and hypothalamic projections to the nucleus of the solitary tract.
作者信息
Holt Marie K, Valderrama Natalia, Polanco Maria J, Hayter Imogen, Badenoch Ellena G, Trapp Stefan, Rinaman Linda
机构信息
Florida State University, Department of Psychology and Program in Neuroscience, Tallahassee, FL, USA; Centre for Cardiovascular and Metabolic Neuroscience, Department of Neuroscience, Physiology & Pharmacology, UCL, London, UK; University of Warwick, School of Life Sciences, Coventry, UK.
Florida State University, Department of Psychology and Program in Neuroscience, Tallahassee, FL, USA.
出版信息
Mol Metab. 2025 Jan;91:102076. doi: 10.1016/j.molmet.2024.102076. Epub 2024 Nov 25.
Stress-induced behaviours are driven by complex neural circuits and some neuronal populations concurrently modulate diverse behavioural and physiological responses to stress. Glucagon-like peptide-1 (GLP-1)-producing preproglucagon (PPG) neurons within the lower brainstem caudal nucleus of the solitary tract (cNTS) are particularly sensitive to stressful stimuli and are implicated in multiple physiological and behavioural responses to interoceptive and psychogenic threats. However, the afferent inputs driving stress-induced activation of PPG neurons are largely unknown, and the role of PPG neurons in anxiety-like behaviour is controversial. Through chemogenetic manipulations we reveal that cNTS PPG neurons have the ability to moderately increase anxiety-like behaviours in mice in a sex-dependent manner. Using an intersectional approach, we show that input from the paraventricular nucleus of the hypothalamus (PVN) drives activation of both the cNTS as a whole and PPG neurons in particular in response to acute restraint stress, but that while this input is rich in corticotropin-releasing hormone (CRH), PPG neurons do not express significant levels of receptors for CRH and are not activated following lateral ventricle delivery of CRH. Finally, we demonstrate that cNTS-projecting PVN neurons are necessary for the ability of restraint stress to suppress food intake in male mice. Our findings reveal sex differences in behavioural responses to PPG neural activation and highlight a hypothalamic-brainstem pathway in stress-induced hypophagia.
应激诱导的行为由复杂的神经回路驱动,一些神经元群体同时调节对压力的多种行为和生理反应。位于延髓尾部孤束核(cNTS)内产生胰高血糖素样肽-1(GLP-1)的前胰高血糖素(PPG)神经元对压力刺激特别敏感,并参与对体内感受性和心理性威胁的多种生理和行为反应。然而,驱动应激诱导的PPG神经元激活的传入输入在很大程度上尚不清楚,并且PPG神经元在焦虑样行为中的作用存在争议。通过化学遗传学操作,我们发现cNTS PPG神经元有能力以性别依赖的方式适度增加小鼠的焦虑样行为。使用交叉方法,我们表明来自下丘脑室旁核(PVN)的输入驱动整个cNTS特别是PPG神经元在急性束缚应激下的激活,但是虽然这种输入富含促肾上腺皮质激素释放激素(CRH),PPG神经元不表达显著水平的CRH受体,并且在侧脑室注射CRH后不会被激活。最后,我们证明投射到cNTS的PVN神经元对于束缚应激抑制雄性小鼠食物摄入的能力是必需的。我们的研究结果揭示了对PPG神经激活的行为反应中的性别差异,并突出了应激诱导的食欲减退中的下丘脑-脑干通路。