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Two Studies Offer Insights Into Interoception of Basic Physiological States and Upper Airway Defenses

drawing of brain with insular cortex highlighted

Two recent studies in mice provide insights into interoception (perception and regulation of signals from inside the body, such as respiration, hunger, etc.). Findings from the first study, which was published in the journal Cell, shed light on airway defense mechanisms and how the brain detects and responds to internal sensations by suggesting that a group of throat-innervating sensory neurons serve as a front-line defense in the upper airways against infiltration and injury within the respiratory tract. The second study, which was published in the journal Neuron, found that insular cortex ongoing activity patterns reliably tracked the gradual return to homeostasis but not changes in behavior. Both studies were supported by the National Center for Complementary and Integrative Health, a component of the National Institutes of Health (NIH), and the NIH Director’s Pioneer Award Program.

In the first study, scientists scanned different cell types within the vagus nerve and looked at gene expression in more than 46,000 individual cells, which revealed at least 37 distinct classes of sensory neurons, each with potentially different functions and responsibilities. By applying optogenetics, a technique in which neurons are genetically modified to respond to light, the researchers were able to selectively activate each class of laryngeal vagal neurons and observe the resulting reflex. They found that neurons expressing one gene in particular, P2RY1, strongly and immediately evoked a coordinated airway defense program. When P2RY1 neurons were selectively eliminated, water and acid no longer evoked airway defense reflexes, while salt and force continued to do so, suggesting that P2RY1 neurons specifically sense and respond to water and acid.

In the second study, scientists imaged mouse insular cortical neurons during hunger and thirst, two physiological deficiency states. The researchers observed that during natural hunger or thirst, food or water cues rapidly and transiently shifted insular cortex population activity to satiety-related patterns. During artificial hunger or thirst, food or water cues further shifted activity beyond the current satiety-related pattern. These findings, combined with circuit-mapping experiments, suggest that the insular cortex integrates visceral sensory signals of current physiological state with hypothalamus-gated amygdala inputs that signal upcoming ingestion of food or water to compute a prediction of future physiological state.


  • Prescott SL, Umans BD, Williams EK, et al. An airway protection program revealed by sweeping genetic control of vagal afferents. Cell. 2020;181:574-589.
  • Livneh Y, Sugden AU, Madara JC, et al. Estimation of current and future physiological states in insular cortex. Neuron. 2020;105:1094-1111.

Publication Date: April 6, 2020