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Torregrossa, A.-M.

Publications and source records attributed to Torregrossa, A.-M..

3 recordsLinked to original sources

Drinking microstructure analysis of direct controls of water intake in male and female rats.

Measures of rodent drinking (lick) patterns are used to test how various manipulations affect fluid intake. Decades of research indicate that manipulating the satiating potency of a stimulus affects the number of licking bursts whereas manipulating the hedonic value of the solution affects the size of the licking bursts or rate of licking. This type of analysis has been largely applied to manipulations that modulate drinking that is already occurring (i.e., indirect controls or modulators of intake), but there is a dearth of studies with detailed measures of licking in response to stimuli that are primary drivers of intake (i.e., direct controls). A better understanding of licking behavior in response to direct controls of fluid intake could provide insight into how drinking is stimulated. Accordingly, we analyzed lick patterns after varying doses of primary drivers (direct controls) of intake, angiotensin II, hypertonic saline, or carbochol, in male and female rats. As expected, all treatments dose-dependently increased licks for water. Analysis of licking patterns revealed dose-related increases in burst number after treatment with all stimuli, but dose did not predict burst size or lick rate. Together with previous work on licking patterns these data suggest that direct controls of water intake are more related to processes associated with satiety than to changes in hedonic value of the consumed substance.

neuroscience↗

Ancient AMY1 gene duplications primed the amylase locus for adaptive evolution upon the onset of agriculture

Starch digestion is a cornerstone of human nutrition. The amylase genes code for the starch-digesting amylase enzyme. Previous studies suggested that the salivary amylase (AMY1) gene copy number increased in response to agricultural diets. However, the lack of nucleotide resolution of the amylase locus hindered detailed evolutionary analyses. Here, we have resolved this locus at nucleotide resolution in 98 present-day humans and identified 30 distinct haplotypes, revealing that the coding sequences of all amylase gene copies are evolving under negative selection. The phylogenetic reconstruction suggested that haplotypes with three AMY1 gene copies, prevalent across all continents and constituting about 70% of observed haplotypes, originated before the out-of-Africa migrations of ancestral modern humans. Using thousands of unique 25 base pair sequences across the amylase locus, we showed that additional AMY1 gene copies existed in the genomes of four archaic hominin genomes, indicating that the initial duplication of this locus may have occurred as far back 800,000 years ago. We similarly analyzed 73 ancient human genomes dating from 300 - 45,000 years ago and found that the AMY1 copy number variation observed today existed long before the advent of agriculture ([~]10,000 years ago), predisposing this locus to adaptive increase in the frequency of higher amylase copy number with the spread of agriculture. Mechanistically, the common three-copy haplotypes seeded non-allelic homologous recombination events that appear to be occurring at one of the fastest rates seen for tandem repeats in the human genome. Our study provides a comprehensive population-level understanding of the genomic structure of the amylase locus, identifying the mechanisms and evolutionary history underlying its duplication and copy number variability in relation to the onset of agriculture.

evolutionary biology↗

Multiple PLCβ signaling pathways in taste receptor cells contribute to the detection of bitter, sweet and umami stimuli

Taste receptor cells use multiple signaling pathways to detect chemicals in potential food items. These cells are functionally grouped into different types: Type I cells act as support cells and have glial-like properties; Type II cells detect bitter, sweet, and umami taste stimuli; and Type III cells detect sour and salty stimuli. We have identified a new population of taste cells that are broadly tuned to multiple taste stimuli including bitter, sweet, sour and umami. The goal of this study was to characterize these broadly responsive (BR) taste cells. We used an IP3R3-KO mouse (does not release calcium (Ca2+) from Type II cells when stimulated with bitter, sweet or umami stimuli) to characterize the BR cells without any potentially confounding input from Type II cells. Using live cell Ca2+ imaging in isolated taste cells from the IP3R3-KO mouse, we found that BR cells are a subset of Type III cells that respond to sour stimuli but also use a PLC{beta}3 signaling pathway to respond to bitter, sweet and umami stimuli. Unlike Type II cells, individual BR cells are broadly tuned and respond to multiple stimuli across different taste modalities. Live cell imaging in a PLC{beta}3-KO mouse confirmed that BR cells use a PLC{beta}3 signaling pathway to generate Ca2+ signals to bitter, sweet and umami stimuli. Analysis of c-Fos activity in the nucleus of the solitary tract (NTS) and short term behavioral assays revealed that BR cells make significant contributions to taste.

neuroscience↗