Chemosensory modulation of neural circuits for sodium appetite.

Abstract

Sodium is the main cation in the extracellular fluid that regulates various physiological functions. Sodium-depletion in the body elevates the hedonic value of sodium taste, which drives animals toward sodium consumption 1,2. Conversely, oral sodium detection rapidly promotes satiation of sodium appetite 3,4, suggesting that chemosensory signals have a central role in sodium appetite and its satiety. Nevertheless, the neural basis of chemosensory-based appetite regulation remains poorly understood. Here, we dissect genetically-defined neural circuits in mice that control sodium intake by integrating sodium taste and internal depletion signals. We show that a subset of excitatory neurons in the pre-locus coeruleus (pre-LC) that express prodynorphin (PDYN) serve as a critical neural substrate for sodium intake behavior. Acute stimulation of this population triggered robust sodium ingestion even from rock salt by transmitting negative valence signals. Inhibition of the same neurons selectively reduced sodium consumption. We further demonstrate that peripheral chemosensory signals rapidly suppressed these sodium appetite neurons. Simultaneous in vivo optical recording and gastric infusion revealed that sensory detection of sodium, but not sodium ingestion per se, is required for the acute modulation of pre-LC PDYN neurons and satiety of sodium appetite. Moreover, retrograde virus tracing showed that sensory modulation is partly mediated by specific GABAergic neurons in the bed nucleus of the stria terminalis. This inhibitory neural population is activated upon sodium ingestion, and sends rapid inhibitory signals to sodium appetite neurons. Together, this study reveals a dynamic circuit diagram that integrates chemosensory signals and the internal need to maintain sodium balance.