Mammalian taste buds are comprised of specialized neuroepithelial cells that act as sensors for molecules that provide nutrition (e.g., carbohydrates, amino acids, and salts) and those that are potentially harmful (e.g., certain plant compounds and strong acids). Type II and III taste bud cells (TBCs) detect molecules described by humans as "sweet," "bitter," "umami," and "sour." TBCs that detect metallic ions, described by humans as "salty," are undefined. Historically, type I glial-like TBCs have been thought to play a supportive role in the taste bud, but little research has been done to explore their role in taste transduction. Some evidence implies that type I cells may detect sodium (Na 1 ) via an amiloride-sensitive mechanism, suggesting they play a role in Na 1 taste transduction. We used an optogenetic approach to study type I TBCs by driving the expression of the light-sensitive channelrhodopsin-2 (ChR2) in type I GAD65 1 TBCs of male and female mice. Optogenetic stimulation of GAD65 1 TBCs increased chorda tympani nerve activity and activated gustatory neurons in the rostral nucleus tractus solitarius. "N neurons," whose NaCl responses were blocked by the amiloride analog benzamil, responded robustly to light stimulation of GAD65 1 TBCs on the anterior tongue. Two-bottle preference tests were conducted under Na 1 -replete and Na 1 -deplete conditions to assess the behavioral impact of optogenetic stimulation of GAD65 1 TBCs. Under Na 1 -deplete conditions GAD65-ChR2-EYFP mice displayed a robust preference for H 2 O illuminated with 470 nm light versus nonilluminated H 2 O, suggesting that type I glial-like TBCs are sufficient for driving a behavior that resembles Na 1 appetite.

Sodium (Na+) is crucial for numerous homeostatic processes in the body and, consequentially, its levels are tightly regulated by multiple organ systems. Sodium is acquired from the diet, commonly in the form of NaCl (table salt), and substances that contain sodium taste salty and are innately palatable at concentrations that are advantageous to physiological homeostasis. The importance of sodium homeostasis is reflected by sodium appetite, an “all-hands-on-deck” response involving the brain, multiple peripheral organ systems, and endocrine factors, to increase sodium intake and replenish sodium levels in times of depletion. Visceral sensory information and endocrine signals are integrated by the brain to regulate sodium intake. Dysregulation of the systems involved can lead to sodium overconsumption, which numerous studies have considered causal for the development of diseases, such as hypertension. The purpose here is to consider the inverse—how disease impacts sodium intake, with a focus on stress-related and cardiometabolic diseases. Our proposition is that such diseases contribute to an increase in sodium intake, potentially eliciting a vicious cycle toward disease exacerbation. First, we describe the mechanism(s) that regulate each of these processes independently. Then, we highlight the points of overlap and integration of these processes. We propose that the analogous neural circuitry involved in regulating sodium intake and blood pressure, at least in part, underlies the reciprocal relationship between neural control of these functions. Finally, we conclude with a discussion on how stress-related and cardiometabolic diseases influence these circuitries to alter the consumption of sodium.

The worldwide prevalence of hypertension continues to rise, shortening lifespan and contributing to the risk of cardiovascular disease and stroke. Although there are numerous contributing risk factors, social adversity is believed to be one that may account, in part, for disparities in rates and treatment outcomes. We have recently begun to evaluate whether chronic social defeat stress (CSDS) can effectively model aspects of stress-induced cardiovascular disease. Adult male C57BL/6J mice were implanted with telemetry devices that recorded blood pressure, heart rate, core body temperature, and activity. Male CD1 mice were used to defeat C57BL/6J mice 1h before the onset of the dark cycle. Immediately following submission, the defeated mouse was housed in the same cage as the aggressor, physically separated by a perforated divider that allows for continuous visual, auditory, and olfactory contact. The C57BL/6J mouse was defeated and housed with a different CD1 mouse each day, to reduce the likelihood of habituation. Initial social defeat resulted in significant increases in blood pressure, activity, and temperature in comparison with control mice. Interestingly, while blood pressure returned to basal levels by the start of the light cycle for the first few days of defeat, chronic social defeat resulted in sustained elevations in blood pressure, lower activity and lower body temperature. Mice exposed to CSDS also exhibited anxiety-like behaviors, spending significantly more time in the closed arms of the elevated plus maze and less time in the center of an open field arena. At the end of the experiment, flow cytometry was performed on spleen and lung tissue from a subset of mice. Splenomegaly was observed in CSDS mice, with an increase in CD11b and monocytic and polymorphonuclear myeloid-derived suppressor cells (M-MDSCs and PMN-MDSCs), consistent with chronic inflammation. There were significant increases in PMN-MDSCs isolated from lung, a strong predictor of pulmonary hypertension, as well as enhanced immunosuppressive capability of MDSCs which is associated with the severity of disease. CSDS also resulted in increases in body, heart and adrenal weights and fluid retention. These data suggest that CSDS may be useful for modeling aspects of hypertension and immune dysfunction induced by chronic social stress, thereby enabling us to better understand the mechanisms that contribute to cardiovascular disease. R35HL150750 This is the full abstract presented at the American Physiology Summit 2023 meeting and is only available in HTML format. There are no additional versions or additional content available for this abstract. Physiology was not involved in the peer review process.