Department of Molecular Physiology and Biophysics, Vanderbilt University School of Medicine, Nashville, United States.
Department of Pharmacology, University of Virginia School of Medicine, Charlottesville, United States.
Elife. 2020 Nov 18;9:e59857. doi: 10.7554/eLife.59857.
The nucleus of the solitary tract (NTS) is critical for the central integration of signals from visceral organs and contains preproglucagon (PPG) neurons, which express leptin receptors in the mouse and send direct projections to the paraventricular nucleus of the hypothalamus (PVH). Here, we visualized projections of PPG neurons in leptin-deficient mice and found that projections from PPG neurons are elevated compared with controls, and PPG projections were normalized by targeted rescue of leptin receptors in mice, which lack functional neuronal leptin receptors. Moreover, and mice displayed increased levels of neuronal activation in the PVH following vagal stimulation, and whole-cell patch recordings of GLP-1 receptor-expressing PVH neurons revealed enhanced excitatory neurotransmission, suggesting that leptin acts cell autonomously to suppress representation of excitatory afferents from PPG neurons, thereby diminishing the impact of visceral sensory information on GLP-1 receptor-expressing neurons in the PVH.
孤束核（NTS）对于内脏器官信号的中枢整合至关重要，其中包含前胰高血糖素（PPG）神经元，这些神经元在小鼠中表达瘦素受体，并向下丘脑室旁核（PVH）发出直接投射。在这里，我们可视化了瘦素缺乏小鼠中 PPG 神经元的投射，发现与对照组相比，PPG 神经元的投射增加，并且通过靶向拯救缺乏功能性神经元瘦素受体的小鼠中的瘦素受体，PPG 投射得到了正常化。此外，和 小鼠在迷走神经刺激后显示出 PVH 中神经元激活水平增加，并且表达 GLP-1 受体的 PVH 神经元的全细胞膜片钳记录显示兴奋性神经传递增强，表明瘦素自主作用以抑制来自 PPG 神经元的兴奋性传入的代表，从而减少内脏感觉信息对 PVH 中表达 GLP-1 受体的神经元的影响。
