No abstract

Activation of stretch-sensitive baroreceptor neurons exerts acute control over heart rate and blood pressure. Although this homeostatic baroreflex has been described for over 80 years, the molecular identity of baroreceptor mechanosensitivity remains unknown. We discovered that mechanically activated ion channels PIEZO1 and PIEZO2 are together required for baroreception. Genetic ablation of both Piezo1 and Piezo2 in the nodose and petrosal sensory ganglia abolished drug-induced baroreflex and aortic depressor nerve activity. Awake, behaving animals that lack Piezos had labile hypertension and increased blood pressure variability, consistent with phenotypes in baroreceptor-denervated animals and humans with baroreflex failure. Optogenetic activation of Piezo2+ sensory afferents was sufficient to initiate baroreflex in mice. These findings suggest that PIEZO1 and PIEZO2 are the long-sought baroreceptor mechanosensors critical for acute blood-pressure control.

Summary Animals can detect and consume nutritive sugars without the influence of taste. However, the identity of the taste-independent nutrient sensor and the mechanism by which animals respond to the nutritional value of sugar are unclear. Here, we report that six neurosecretory cells in the Drosophila brain that produce Diuretic hormone 44 (Dh44), a homologue of the mammalian corticotropin-releasing hormone (CRH), were specifically activated by nutritive sugars. Flies in which the activity of these neurons or the expression of Dh44 was disrupted failed to select nutritive sugars. Manipulation of the function of Dh44 receptors had a similar effect. Notably, artificial activation of Dh44 receptor-1 neurons resulted in proboscis extensions, and frequent episodes of excretion. Conversely, reduced Dh44 activity led to decreased excretion. Together, these actions facilitate ingestion and digestion of nutritive foods. We propose that the Dh44 system directs the detection and consumption of nutritive sugars through a positive feedback loop.

Feeding behavior is influenced primarily by two factors: nutritional needs and food palatability. However, the role of food deprivation and metabolic needs in the selection of appropriate food is poorly understood. Here, we show that the fruit fly, Drosophila melanogaster, selects calorie-rich foods following prolonged food deprivation in the absence of taste-receptor signaling. Flies mutant for the sugar receptors Gr5a and Gr64a cannot detect the taste of sugar, but still consumed sugar over plain agar after 15 h of starvation. Similarly, pox-neuro mutants that are insensitive to the taste of sugar preferentially consumed sugar over plain agar upon starvation. Moreover, when given a choice between metabolizable sugar (sucrose or D-glucose) and nonmetabolizable (zero-calorie) sugar (sucralose or L-glucose), starved Gr5a; Gr64a double mutants preferred metabolizable sugars. These findings suggest the existence of a taste-independent metabolic sensor that functions in food selection. The preference for calorie-rich food correlates with a decrease in the two main hemolymph sugars, trehalose and glucose, and in glycogen stores, indicating that this sensor is triggered when the internal energy sources are depleted. Thus, the need to replenish depleted energy stores during periods of starvation may be met through the activity of a taste-independent metabolic sensing pathway.F ood quantity and quality can vary greatly in natural habitats. To survive such variations, animals must be able to search for and detect appropriate food sources under all conditions, especially during times of food scarcity. Peripheral chemosensory neurons, such as sugar taste neurons, allow animals to detect palatable foods (1-5). Additional mechanisms may be necessary for the detection of foods to meet acute nutritional needs. Indeed, animals learn to positively associate a flavor paired with intragastric sugar infusion (6). Recently, studies of Trpm5 −/− mice, which are insensitive to the taste of sugar, also have revealed that these animals develop a preference for a sugar solution on the basis of its caloric content even in the absence of gustatory input (7). Unfortunately, the nature of such mechanisms is currently unknown. It is also not clear whether they function under starvation conditions. To search for mechanisms by which animals can respond to the caloric content of food independently of orosensory cues, we studied the effect of starvation on food choice in Drosophila mutants that are unable to taste sugar. Specifically, we sought to determine whether food-deprived flies carrying mutations in Gr5a and Gr64a (3-5), the sugar receptor genes, and in poxneuro (poxn) (8-10), a gene that specifies chemosensory neurons, develop a preference for the caloric content of sugars in the absence of taste perception. We found that these mutant flies demonstrated a preference for caloric food upon starvation and that this preference correlated with the energy needs of the fly. Furthermore, wild-type (WT) flies showed a shift in preference to metab...