• 向小鼠肠道注水引起的肠道低渗透压,可激活肠-脑途径中的迷走神经(而非背根神经节)的特定神经亚群;
  • 肝门区(HPA)是传递渗透压信号的主要区域,阻断支配该区域的迷走神经分支可消除迷走神经对肠道低渗的反应;
  • 通过小鼠行为实验和对大脑口渴神经元活动的记录表明,源自HPA的渗透压信号对于饮水后的口渴消除是必须的;
  • 该信号由血管活性肠肽(VIP,一种激素)介导,小鼠饮水后,VIP被分泌到门静脉,进而激活HPA的迷走神经。
Nature [IF:69.504]

Sensory representation and detection mechanisms of gut osmolality change



2022-01-26, Article

Abstract & Authors:展开

Ingested food and water stimulate sensory systems in the oropharyngeal and gastrointestinal areas before absorption1,2. These sensory signals modulate brain appetite circuits in a feed-forward manner3,4,5. Emerging evidence suggests that osmolality sensing in the gut rapidly inhibits thirst neurons upon water intake. Nevertheless, it remains unclear how peripheral sensory neurons detect visceral osmolality changes, and how they modulate thirst. Here we use optical and electrical recording combined with genetic approaches to visualize osmolality responses from sensory ganglion neurons. Gut hypotonic stimuli activate a dedicated vagal population distinct from mechanical-, hypertonic- or nutrient-sensitive neurons. We demonstrate that hypotonic responses are mediated by vagal afferents innervating the hepatic portal area (HPA), through which most water and nutrients are absorbed. Eliminating sensory inputs from this area selectively abolished hypotonic but not mechanical responses in vagal neurons. Recording from forebrain thirst neurons and behavioural analyses show that HPA-derived osmolality signals are required for feed-forward thirst satiation and drinking termination. Notably, HPA-innervating vagal afferents do not sense osmolality itself. Instead, these responses are mediated partly by vasoactive intestinal peptide secreted after water ingestion. Together, our results reveal visceral hypoosmolality as an important vagal sensory modality, and that intestinal osmolality change is translated into hormonal signals to regulate thirst circuit activity through the HPA pathway.

First Authors:
Takako Ichiki

Correspondence Authors:
Yuki Oka

All Authors:
Takako Ichiki,Tongtong Wang,Ann Kennedy,Allan-Hermann Pool,Haruka Ebisu,David J Anderson,Yuki Oka

Nature Reviews Gastroenterology and Hepatology期刊

Detecting gut osmolality changes to quench thirst