The Neural Basis of Sodium Appetite

Author: Lee, Sangjun

Year: 2020

Degree: Dissertation (Ph.D.)

Advisor: Oka, Yuki

Committee Members: Lester, Henry A.; Anderson, David J.; Lois, Carlos; Oka, Yuki

Option: Neurobiology

DOI: 10.7907/bcxa-s404

Abstract

Fluid homeostasis, which maintains a stable internal environment, is critical for survival. Body fluid is tightly monitored and regulated through its main components, water and salt. Here, I focus on the aspect of sodium regulation when sodium is the main cation in the extracellular fluid and is also required for primary metabolism. The depletion of sodium induces the retention of sodium but also a central mechanism to obtain sodium from the external sources. This need for sodium specifically drives animals towards sodium consumption, called sodium appetite. Even though sodium appetite is specific for only sodium ion, sodium appetite observed as an innate behavior across the animal kingdom.

Sodium appetite is strictly regulated by both peripheral sensory signals and central appetite signals. Due to the development of genetic tools, I was able to investigate the neural basis of sodium appetite from searching sodium appetite dedicated neurons. Here, I identify two genetically defined neural circuits in mice that control sodium intake. The activation of these neurons drives robust sodium intake in sated animals. Particularly, prodynorphin expressing neurons in the pre-locus coeruleus shown specific consumption to sodium compounds, including rock salt. In terms of loss-of-function, inhibition of these neurons selectively reduced sodium consumption. It was further shown that these neurons receive sodium depleted signals by aldosterone-sensitive neurons.

Previously, it was suggested that taste signals have a central role in sodium satiation. I demonstrate that the oral detection of sodium rapidly suppresses sodium appetite neurons. The blockage of the sodium taste or gastric infusion of sodium abolished the sodium suppression in the sodium appetite neurons. Consistently, gastric infusion of sodium did not cause sodium satiation. Moreover, retrograde-viral methods showed that specific inhibitory neurons partially mediate sensory modulation in the bed nucleus of the stria terminalis.

Together, I identified a specific neural population as a functional unit for sodium appetite. By knowing the dedicated circuits for sodium appetite, I demonstrated chemosensory and physiological signals regulate the neural circuits. The genetically defined neural population can be handle as an entry point of further investigation of the neural basis of sodium appetite.

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