Wang David C, Wu Yunming, Mehaffy Conor, Espinoza-Campomanes Leslie A, Santos-Valencia Fernando, Franks Kevin M, Luo Liqun
Howard Hughes Medical Institute.
Department of Biology, Stanford University.
bioRxiv. 2025 Feb 13:2024.09.22.614378. doi: 10.1101/2024.09.22.614378.
Hunger and thirst are two fundamental drives for maintaining homeostasis and elicit distinct food- and water-seeking behaviors essential for survival. For neonatal mammals, however, both hunger and thirst are sated by consuming milk from their mother. While distinct neural circuits underlying hunger and thirst drives in the adult brain have been characterized, it is unclear when these distinctions emerge in neonates and what processes may affect their development. Here we show that hypothalamic hunger and thirst regions already exhibit specific responses to starvation and dehydration well before a neonatal mouse can seek food and water separately. At this early age, hunger neurons drive feeding behaviors more than do thirst neurons. Neuropixels recordings in dehydrated and starved neonatal mice revealed that maternal presentation leads to a relative increase in activity which is suppressed by feeding on short timescales, particularly in hypothalamic and thalamic neurons. Changes in activity become more heterogeneous on longer timescales. Lastly, within neonatal regions that respond to both hunger and thirst, subpopulations of neurons respond distinctly to one or the other need. Combining food and water into a liquid diet throughout the animal's life does not alter the distinct representations of hunger and thirst in the adult brain. Thus, neural representations of hunger and thirst in mice become distinct before food- and water-seeking behaviors mature and are robust to environmental changes in food and water sources.
饥饿和口渴是维持体内平衡的两种基本驱动力，会引发对生存至关重要的独特觅食和饮水行为。然而，对于新生哺乳动物来说，饥饿和口渴都通过吸食母乳来满足。虽然成年大脑中饥饿和口渴驱动力背后的不同神经回路已得到表征，但尚不清楚这些差异在新生儿中何时出现，以及哪些过程可能影响其发育。在这里，我们表明，在新生小鼠能够分别觅食和饮水之前，下丘脑的饥饿和口渴区域就已经对饥饿和脱水表现出特定反应。在这个早期阶段，饥饿神经元比口渴神经元更能驱动进食行为。对脱水和饥饿的新生小鼠进行的神经像素记录显示，母鼠的出现会导致活动相对增加，而在短时间尺度上，进食会抑制这种增加，特别是在下丘脑和丘脑神经元中。在较长时间尺度上，活动变化变得更加不均匀。最后，在对饥饿和口渴都有反应的新生区域内，神经元亚群对其中一种或另一种需求有明显不同的反应。在动物的一生中，将食物和水混合成流质饮食并不会改变成年大脑中饥饿和口渴的不同表征。因此，小鼠饥饿和口渴的神经表征在觅食和饮水行为成熟之前就已变得不同，并且对食物和水源的环境变化具有鲁棒性。
