Sweet Serena R, Biddinger Jessica E, Zimmermann Jessie B, Yu Gina L, Simerly Richard B
Department of Molecular Physiology & Biophysics, Vanderbilt University, Nashville, TN 37232, USA.
Vanderbilt Center for Addiction Research, Vanderbilt University, Nashville, TN 37232, USA.
iScience. 2025 Mar 24;28(5):112284. doi: 10.1016/j.isci.2025.112284. eCollection 2025 May 16.
Drinking and feeding are tightly coordinated homeostatic events and the paraventricular nucleus of the hypothalamus (PVH) represents a possible node of neural integration for signals related to energy and fluid homeostasis. We used mice and Fos labeling to visualize neurons in the PVH and median preoptic nucleus (MEPO) responding to both water deprivation and feeding signals. We determined that structural and functional development of dehydration-sensitive inputs to the PVH precedes those of agouti-related peptide (AgRP) neurons, which convey hunger signals and are known to be developmentally programmed by nutrition. Moreover, we found that osmotic hyperstimulation of neonatal mice led to enhanced AgRP inputs to the PVH in adulthood, as well as disruptions to ingestive behaviors during high-fat diet feeding and dehydration-anorexia. Thus, development of feeding circuits is impacted not only by nutritional signals, but also by early perturbations to fluid homeostasis with context-specific consequences for coordination of ingestive behavior.
饮水和进食是紧密协调的稳态过程，下丘脑室旁核（PVH）可能是与能量和液体稳态相关信号的神经整合节点。我们使用小鼠和Fos标记来可视化PVH和视前正中核（MEPO）中对缺水和进食信号有反应的神经元。我们确定，PVH脱水敏感输入的结构和功能发育先于刺鼠相关肽（AgRP）神经元，AgRP神经元传递饥饿信号，并且已知其发育受营养编程。此外，我们发现新生小鼠的渗透性高刺激会导致成年后AgRP对PVH的输入增强，以及高脂饮食喂养和脱水厌食期间摄食行为的紊乱。因此，进食回路的发育不仅受到营养信号的影响，还受到早期液体稳态扰动的影响，对摄食行为的协调产生特定背景下的后果。
