Ryan Philip J, Ross Silvano I, Campos Carlos A, Derkach Victor A, Palmiter Richard D
Howard Hughes Medical Institute, University of Washington, Seattle, Washington, USA.
Department of Biochemistry, University of Washington, Seattle, Washington, USA.
Nat Neurosci. 2017 Dec;20(12):1722-1733. doi: 10.1038/s41593-017-0014-z. Epub 2017 Nov 13.
Brain regions that regulate fluid satiation are not well characterized, yet are essential for understanding fluid homeostasis. We found that oxytocin-receptor-expressing neurons in the parabrachial nucleus of mice (Oxtr neurons) are key regulators of fluid satiation. Chemogenetic activation of Oxtr neurons robustly suppressed noncaloric fluid intake, but did not decrease food intake after fasting or salt intake following salt depletion; inactivation increased saline intake after dehydration and hypertonic saline injection. Under physiological conditions, Oxtr neurons were activated by fluid satiation and hypertonic saline injection. Oxtr neurons were directly innervated by oxytocin neurons in the paraventricular hypothalamus (Oxt neurons), which mildly attenuated fluid intake. Activation of neurons in the nucleus of the solitary tract substantially suppressed fluid intake and activated Oxtr neurons. Our results suggest that Oxtr neurons act as a key node in the fluid satiation neurocircuitry, which acts to decrease water and/or saline intake to prevent or attenuate hypervolemia and hypernatremia.
调节体液饱腹感的脑区尚未得到充分表征,但对于理解体液平衡至关重要。我们发现,小鼠臂旁核中表达催产素受体的神经元(Oxtr神经元)是体液饱腹感的关键调节因子。对Oxtr神经元进行化学遗传学激活可强烈抑制无热量液体摄入,但不会减少禁食后的食物摄入量或盐耗竭后的盐摄入量;失活则会增加脱水和注射高渗盐水后的盐水摄入量。在生理条件下,Oxtr神经元会因体液饱腹感和注射高渗盐水而被激活。Oxtr神经元直接受下丘脑室旁核中的催产素神经元(Oxt神经元)支配,后者会轻微减弱液体摄入。激活孤束核中的神经元可显著抑制液体摄入并激活Oxtr神经元。我们的结果表明,Oxtr神经元是体液饱腹感神经回路中的关键节点,其作用是减少水和/或盐水摄入,以预防或减轻血容量过多和高钠血症。