Sweet taste signaling and the formation of memories of energy sources

The last decade witnessed remarkable advances in our knowledge of the gustatory system. Application of molecular biology techniques not only determined the identity of the membrane receptors and downstream effectors that mediate sweetness, but also uncovered the overall logic of gustatory coding in the periphery. However, while the ability to taste sweet may offer the obvious advantage of eliciting rapid and robust intake of sugars, a number of recent studies demonstrate that sweetness is neither necessary nor sufficient for the formation of long-lasting preferences for stimuli associated with sugar intake. Furthermore, uncoupling sweet taste from ensuing energy utilization may disrupt body weight control. This minireview examines recent experiments performed in both rodents and Drosophila revealing the taste-independent rewarding properties of metabolizable sugars. Taken together, these experiments demonstrate the reinforcing actions of sugars in the absence of sweet taste signaling and point to a critical role played by dopamine systems in translating metabolic sensing into behavioral action. From a mechanistic viewpoint, current evidence favors the concept that gastrointestinal and post-absorptive signals contribute in parallel to sweet-independent sugar acceptance and dopamine release

Sweet Taste Signaling Functions as a Hypothalamic Glucose Sensor

Brain glucosensing is essential for normal body glucose homeostasis and neuronal function. However, the exact signaling mechanisms involved in the neuronal sensing of extracellular glucose levels remain poorly understood. Of particular interest is the identification of candidate membrane molecular sensors that would allow neurons to change firing rates independently of intracellular glucose metabolism. Here we describe for the first time the expression of the taste receptor genes Tas1r1, Tas1r2 and Tas1r3, and their associated G-protein genes, in the mammalian brain. Neuronal expression of taste genes was detected in different nutrient-sensing forebrain regions, including the paraventricular and arcuate nuclei of the hypothalamus, the CA fields and dentate gyrus of the hippocampus, the habenula, and cortex. Expression was also observed in the intra-ventricular epithelial cells of the choroid plexus. These same regions were found to express the corresponding gene products that form the heterodimeric T1R2/T1R3 and T1R1/T1R3 sweet and l-amino acid taste G-protein coupled receptors, respectively, along with the taste G-protein α-gustducin. Moreover, in vivo studies in mice demonstrated that the hypothalamic expression of taste-related genes is regulated by the nutritional state of the animal, with food deprivation significantly increasing expression levels of Tas1r1 and Tas1r2 in hypothalamus, but not in cortex. Furthermore, exposing mouse hypothalamic cells to a low-glucose medium, while maintaining normal l-amino acid concentrations, specifically resulted in higher expression levels of the sweet-associated gene Tas1r2. This latter effect was reversed by adding the non-metabolizable artificial sweetener sucralose to the low-glucose medium, indicating that taste-like signaling in hypothalamic neurons does not require intracellular glucose oxidation. Taken together, our findings suggest that the heterodimeric G-protein coupled sweet receptor T1R2/T1R3 is a candidate membrane-bound brain glucosensor

Sugar Metabolism Regulates Flavor Preferences and Portal Glucose Sensing

In most species, including humans, food preference is primarily controlled by nutrient value. In particular, glucose-containing sugars exert exquisitely strong effects on food choice via gut-generated signals. However, the identity of the visceral signals underlying glucose’s rewarding effects remains uncertain. In particular, it is unknown whether sugar metabolism mediates the formation of preferences for glucose-containing sugars. Using the mouse as a model organism, we made use of a combination of conditioning schedules, gastrointestinal nutrient administration, and chromatographic/electrochemical methods to assess the behavioral and neural effects of activating the gut with either metabolizable glucose or a non-metabolizable glucose analog. We show that mice display much superior preferences for flavors associated with intra-gastric infusions of glucose compared to flavors associated with intra-gastric infusions of the non-metabolizable glucose analog α-methyl-D-glucopyranoside (“MDG,” an activator of intestinal sodium/glucose co-transporters). These effects were unaffected by surgical bypassing of the duodenum, suggesting glucose-specific post-absorptive sensing mechanisms. Consistently, intra-portal infusions of glucose, but not of MDG, induced significant rises in dopamine (DA) levels within brain reward circuits. Our data reveal that the unmatched rewarding effects of glucose-containing sugars cannot be accounted for by metabolism-independent activation of sodium/glucose cotransporters; rather, they point to glucose metabolism as the physiological mechanism underlying the potent reward value of sugar-sweetened flavored beverages. In particular, no circulating “gut factors” need to be invoked to explain the reward value of ingested glucose. Thus, instead of circulating gut hormones, portal-mesenteric sensing of glucose emerges as the preferential physiological pathway for sugar reward

The Insular Cortex Controls Food Preferences Independently of Taste Receptor Signaling

The insular cortex (IC) contains the primary sensory cortex for oral chemosensation including gustation, and its integrity is required for appropriate control of feeding behavior. However, it remains unknown whether the role of this brain area in food selection relies on the presence of peripheral taste input. Using multielectrode recordings, we found that the responses of populations of neurons in the IC of freely licking, sweet-blind Trpm5−/− mice are modulated by the rewarding postingestive effects of sucrose. FOS immunoreactivity analyses revealed that these responses are restricted to the dorsal insula. Furthermore, bilateral lesions in this area abolished taste-independent preferences for sucrose that can be conditioned in these Trpm5−/− animals while preserving their ability to detect sucrose. Overall, these findings demonstrate that, even in the absence of peripheral taste input, IC regulates food choices based on postingestive signals

Side-lobe level reduction in bio-inspired optical phased-array antennas

COORDENAÇÃO DE APERFEIÇOAMENTO DE PESSOAL DE NÍVEL SUPERIOR - CAPESFUNDAÇÃO DE AMPARO À PESQUISA DO ESTADO DE SÃO PAULO - FAPESPCONSELHO NACIONAL DE DESENVOLVIMENTO CIENTÍFICO E TECNOLÓGICO - CNPQPhased arrays are expected to play a critical role in visible and infrared wireless systems. Their improved performance compared to single element antennas finds uses in communications, imaging, and sensing. However, fabrication of photonic antennas and their feeding network require long element separation, leading to the appearance of secondary radiation lobes and, consequently, crosstalk and interference. In this work, we experimentally show that by arranging the elements according to the Fermat's spiral, the side lobe level (SLL) can be reduced. This reduction is proved in a CMOS-compatible 8-element array, revealing a SLL decrement of 0.9 dB. Arrays with larger numbers of elements and inter-element spacing are demonstrated through a spatial light modulator (SLM) and an SLL drop of 6.9 dB is measured for a 64-element array. The reduced SLL, consequently, makes the proposed approach a promising candidate for applications in which antenna gain, power loss, or information security are key requirements.25243010530114COORDENAÇÃO DE APERFEIÇOAMENTO DE PESSOAL DE NÍVEL SUPERIOR - CAPESFUNDAÇÃO DE AMPARO À PESQUISA DO ESTADO DE SÃO PAULO - FAPESPCONSELHO NACIONAL DE DESENVOLVIMENTO CIENTÍFICO E TECNOLÓGICO - CNPQCOORDENAÇÃO DE APERFEIÇOAMENTO DE PESSOAL DE NÍVEL SUPERIOR - CAPESFUNDAÇÃO DE AMPARO À PESQUISA DO ESTADO DE SÃO PAULO - FAPESPCONSELHO NACIONAL DE DESENVOLVIMENTO CIENTÍFICO E TECNOLÓGICO - CNPQSem informação08/57857-22013/20180-32015/04113-0574017/2008-9446746/2014-

Fast Matrix Multiplication via Compiler-only Layered Data Reorganization and Intrinsic Lowering

The resurgence of machine learning has increased the demand for high-performance basic linear algebra subroutines (BLAS), which have long depended on libraries to achieve peak performance on commodity hardware. High-performance BLAS implementations rely on a layered approach that consists of tiling and packing layers, for data (re)organization, and micro kernels that perform the actual computations. The creation of high-performance micro kernels requires significant development effort to write tailored assembly code for each architecture. This hand optimization task is complicated by the recent introduction of matrix engines by IBM's POWER10 MMA, Intel AMX, and Arm ME to deliver high-performance matrix operations. This paper presents a compiler-only alternative to the use of high-performance libraries by incorporating, to the best of our knowledge and for the first time, the automatic generation of the layered approach into LLVM, a production compiler. Modular design of the algorithm, such as the use of LLVM's matrix-multiply intrinsic for a clear interface between the tiling and packing layers and the micro kernel, makes it easy to retarget the code generation to multiple accelerators. The use of intrinsics enables a comprehensive performance study. In processors without hardware matrix engines, the tiling and packing delivers performance up to 22x (Intel), for small matrices, and more than 6x (POWER9), for large matrices, faster than PLuTo, a widely used polyhedral optimizer. The performance also approaches high-performance libraries and is only 34% slower than OpenBLAS and on-par with Eigen for large matrices. With MMA in POWER10 this solution is, for large matrices, over 2.6x faster than the vector-extension solution, matches Eigen performance, and achieves up to 96% of BLAS peak performance

Leptin regulates the reward value of nutrient

We developed an assay for quantifying the reward value of nutrient and used it to analyze the effects of metabolic state and leptin. In this assay, mice chose between two sippers, one of which dispensed water and was coupled to optogenetic activation of dopaminergic (DA) neurons and the other of which dispensed natural or artificial sweeteners. This assay measured the reward value of sweeteners relative to lick-induced optogenetic activation of DA neurons. Mice preferred optogenetic stimulation of DA neurons to sucralose, but not to sucrose. However, the mice preferred sucralose plus optogenetic stimulation versus sucrose. We found that food restriction increased the value of sucrose relative to sucralose plus optogenetic stimulation, and that leptin decreased it. Our data suggest that leptin suppresses the ability of sucrose to drive taste-independent DA neuronal activation and provide new insights into the mechanism of leptin's effects on food intake

Mechanisms for Sweetness123

A remarkable amount of information has emerged in the past decade regarding sweet taste physiology. This article reviews these data, with a particular focus on the elucidation of the sweet taste receptor, its location and actions in taste transduction in the mouth, its nontaste functions in the gastrointestinal tract (e.g., in enteroendocrine cells), and the brain circuitry involved in the sensory processing of sweet taste. Complications in the use of rodents to model human sweet taste perception and responses are also considered. In addition, information relating to low-calorie sweeteners (LCS) is discussed in the context of these issues. Particular consideration is given to the known effects of LCS on enteroendocrine cell function

Forced Swim Reliability for Exercise Testing in Rats by a Tethered Swimming Apparatus

To assess the physical capacity of rats in forced swim tests, the animal should perform a continuous activity (CON) at the surface to avoid apnea. Bobbing movement (BOB), vigorous paddling known as climbing (CLI), and diving activity (DIV) are inadequate swimming patterns known to increase the exercise intensity variability, impairing the test reliability. Thus, the exercise work accomplished and related physiological variables, such as the blood lactate concentration, may be unreproducible in forced swim. This study aimed to verify the exercise work reproducibility in rats with a 30-min test–retest at maximal lactate steady state (MLSS) intensity using a tethered-swimming apparatus that analyzes swimming patterns by the direct measurement of swimming force. Additionally, it was determined the swimming force and duration of CON, BOB, CLI, and DIV at physiologically different exercise-intensities. The swimming force at MLSS (n = 64) was 38 ± 7 gf.Kg-1, while the blood lactate concentration was 4.2 ± 1.6 mmol.L-1. In the test–retest (N = 23), swimming force (36.6 ± 7 gf.Kg-1 vs. 36.4 ± 7 gf.Kg-1) and blood lactate concentration (4.7 ± 1.7 mmol.L-1 vs. 4.2 ± 1.7 mmol.l-1) were similar, but only the swimming force was highly correlated (0.90 and 0.31). Although it was not statistically different, the swimming force for CON tends to be slightly lower than CLI and slightly higher than BOB independently of exercise-intensity. The CON pattern predominates (∼52.8 ± 18%) at intensities below and of MLSS but BOB was the swimming pattern more often observed above MLSS-intensity (52.6 ± 18%). The present study used a tethered swimming apparatus to investigate the reliability of forced swim tests for exercise testing in rats and better understand the swimming patterns when determining the MLSS, but the results can be extended to any study that rely on forced swim for exercise testing and training. The result suggests that, at least at intensities of physiological stability, the exercise work accomplished by rats is reproducible in forced swim, but the blood lactate concentration seems to be affected by other factors, such as the apnea and stress caused by the possibility of drowning, besides the exercise-intensity