Activation of lateral hypothalamus-projecting parabrachial neurons by intraorally delivered gustatory stimuli

The present study investigated a subpopulation of neurons in the mouse parabrachial nucleus (PbN), a gustatory and visceral relay area in the brainstem, that project to the lateral hypothalamus (LH). We made injections of the retrograde tracer Fluorogold (FG) into LH, resulting in fluorescent labeling of neurons located in different regions of the PbN. Mice were stimulated through an intraoral cannula with one of seven different taste stimuli, and PbN sections were processed for immunohistochemical detection of the immediate early gene c-Fos, which labels activated neurons. LH projection neurons were found in all PbN subnuclei, but in greater concentration in lateral subnuclei, including the dorsal lateral subnucleus (dl). Fos-like immunoreactivity (FLI) was observed in the PbN in a stimulus-dependent pattern, with the greatest differentiation between intraoral stimulation with sweet (0.5 M sucrose) and bitter (0.003 M quinine) compounds. In particular, sweet and umami-tasting stimuli evoked robust FLI in cells in the dl, whereas quinine evoked almost no FLI in cells in this subnucleus. Double-labeled cells were also found in the greatest quantity in the dl. Overall, these results support the hypothesis that the dl contains direct a projection to the LH that is activated preferentially by appetitive compounds; this projection may be mediated by taste and/or postingestive mechanisms

Genetic Control of a Central Pattern Generator: Rhythmic Oromotor Movement in Mice Is Controlled by a Major Locus near Atp1a2

Fluid licking in mice is a rhythmic behavior that is controlled by a central pattern generator (CPG) located in a complex of brainstem nuclei. C57BL/6J (B6) and DBA/2J (D2) strains differ significantly in water-restricted licking, with a highly heritable difference in rates (h2≥0.62) and a corresponding 20% difference in interlick interval (mean ± SEM = 116.3±1 vs 95.4±1.1 ms). We systematically quantified motor output in these strains, their F1 hybrids, and a set of 64 BXD progeny strains. The mean primary interlick interval (MPI) varied continuously among progeny strains. We detected a significant quantitative trait locus (QTL) for a CPG controlling lick rate on Chr 1 (Lick1), and a suggestive locus on Chr 10 (Lick10). Linkage was verified by testing of B6.D2-1D congenic stock in which a segment of Chr 1 of the D2 strain was introgressed onto the B6 parent. The Lick1 interval on distal Chr 1 contains several strong candidate genes. One of these is a sodium/potassium pump subunit (Atp1a2) with widespread expression in astrocytes, as well as in a restricted population of neurons. Both this subunit and the entire Na+/K+-ATPase molecule have been implicated in rhythmogenesis for respiration and locomotion. Sequence variants in or near Apt1a2 strongly modulate expression of the cognate mRNA in multiple brain regions. This gene region has recently been sequenced exhaustively and we have cataloged over 300 non-coding and synonymous mutations segregating among BXD strains, one or more of which is likely to contribute to differences in central pattern generator tempo

The neural processing of taste

Although there have been many recent advances in the field of gustatory neurobiology, our knowledge of how the nervous system is organized to process information about taste is still far from complete. Many studies on this topic have focused on understanding how gustatory neural circuits are spatially organized to represent information about taste quality (e.g., "sweet", "salty", "bitter", etc.). Arguments pertaining to this issue have largely centered on whether taste is carried by dedicated neural channels or a pattern of activity across a neural population. But there is now mounting evidence that the timing of neural events may also importantly contribute to the representation of taste. In this review, we attempt to summarize recent findings in the field that pertain to these issues. Both space and time are variables likely related to the mechanism of the gustatory neural code: information about taste appears to reside in spatial and temporal patterns of activation in gustatory neurons. What is more, the organization of the taste network in the brain would suggest that the parameters of space and time extend to the neural processing of gustatory information on a much grander scale

Behavioral genetics and taste

This review focuses on behavioral genetic studies of sweet, umami, bitter and salt taste responses in mammals. Studies involving mouse inbred strain comparisons and genetic analyses, and their impact on elucidation of taste receptors and transduction mechanisms are discussed. Finally, the effect of genetic variation in taste responsiveness on complex traits such as drug intake is considered. Recent advances in development of genomic resources make behavioral genetics a powerful approach for understanding mechanisms of taste

Head and Neck Ultrasound Utilization Rates: 2012 to 2019

Abstract Objective We measured utilization of clinician‐performed head and neck ultrasound among otolaryngologists, endocrinologists, and general surgeons, using Medicare Provider Utilization and Payment Data. Study Design Retrospective analysis of Medicare billing database. Setting University. Methods For each year, the files were filtered to include 4 provider types: Diagnostic Radiology (DR), Endocrinology (ENDO), General Surgery (GS), and Otolaryngology (OTO). Billable procedures are listed by Healthcare Common Procedure Coding System code and a filter was applied to include 76536 Ultrasound, soft tissues of the head and neck. Results In 2019, OTOs submitted charges for 2.1% of all head and neck diagnostic ultrasounds (76536) performed on Medicare beneficiaries. For each year 2012 to 2019, DRs submitted the most charges, followed by ENDOs, and then OTO and GS. Charges for all groups increased in a proportional manner across the 8‐year period. 14.5% of OTOs submitted more than 100 charges apiece during 2019, that is, “super users.” The percentage of super users within each specialty increased from 2012 to 2019. Overall, the data support an ever‐increasing use of head and neck ultrasound (HNUS) among all provider types. Conclusion Even with increased use among OTOs, this specialty only accounted for a small percentage of head & neck diagnostic ultrasounds performed on Medicare beneficiaries in 2019. Changes in volume of nonradiology point‐of‐care HNUS was not associated with changes in DR volume. A greater proportion of OTOs than DRs are “super users” among the ultrasound users within their specialty, performing more than 100 exams/year. Level of Evidence V

Modeling time dependencies in bitter coding by C3.SW neurons.

<p>(<b>A</b>) Plots showing sequential, 500 ms wide windows of taste activity (spike density per half-second, ordinates) across 43 C3.SW cells (abscissae) to the highest concentrations of quinine, denatonium, cycloheximide, and sucrose octaacetate. The time window of taste activity captured by each plot is indicated. Legend in <b>B</b> gives the stimulus associated with each colored response for all panels in this figure. (<b>B</b>) Three-dimensional plot showing the outcome of principal components (PC) analysis applied to sequential, 500 ms wide windows of activity across 43 C3.SW neurons during taste stimulation with all concentrations of quinine, denatonium, cycloheximide, sucrose octaacetate, and also water. Response windows from stimulus onset to offset (i.e., 0 to 5 s post stimulus) are represented. For each stimulus, PC-mapped points for sequential response windows are connected using color-coded lines, as in <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0041597#pone-0041597-g006" target="_blank">Figure 6</a>. Arrows indicate flow of contiguous points/response windows; squares mark points for response windows residing 1 to 1.5 s post stimulus onset. Response “paths” for activity to all low, intermediate and high concentrations (legend and <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0041597#pone-0041597-t001" target="_blank">Table 1</a>) of each stimulus are shown; responses to intermediate concentrations are not differentiated. PC1, PC2, and PC3 explain 76% of the total response variance. The general locales of the “start” and “end” points for the trajectories are indicated. (<b>C</b>) Same as panel <b>B</b>, except that activity within each 500 ms window was averaged over concentrations for each stimulus prior to PC analysis, highlighting global trends in the data. PC1, PC2, and PC3 explain 83% of the total response variance.</p

Taste stimuli, concentrations, and abbreviations.

<p>Taste stimuli, concentrations, and abbreviations.</p

Definition of neural clusters.

<p>Groupings of NTS neurons in C3 (<b>A</b>) and C3.SW (<b>B</b>) mice defined by hierarchical clustering of activity to stimuli representative of different taste categories. Y-bars represent mean ± s.e.m. responses (net spikes in 5 s). Dendrograms showing cluster recovery in each line are depicted by insets near the top of each panel. Numbers along the abscissae denote stimuli (legend). In the legend, numbers in stimulus abbreviations indicate concentrations from lowest (e.g., 1) to highest (e.g., 5), where applicable (<a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0041597#pone-0041597-t001" target="_blank">Table 1</a>).</p

Raw response data from taste-sensitive neurons.

<p>Digital oscilloscope sweeps showing electrophysiological activity to all stimuli recorded from two C3.SW cells (A and B) and two C3 neurons (C and D). The C3 neurons were recorded in series from one mouse; C3.SW cells are from different mice. The stimulus tested during each sweep is abbreviated (<a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0041597#pone-0041597-t001" target="_blank">Table 1</a>) along the left margin. Where applicable, numbers in stimulus abbreviations indicate concentrations from lowest (e.g., 1) to highest (e.g., 5), as in <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0041597#pone-0041597-t001" target="_blank">Table 1</a>. Upward and downward arrows at the bottom of each sweep stack indicate stimulus onset and offset, respectively.</p

Neural responses to bitter and other stimuli.

<p>Heatmaps showing the net 5 s response to each of 26 taste stimuli (abscissae) across all 36 C3 (<b>A</b>) and 43 C3.SW (<b>B</b>) neurons (ordinates). The heat scale in panel <b>A</b> gives response spike density for panels <b>A</b> and <b>B</b>. Neurons are sorted within mouse line by cluster analysis of activity to all concentrations of quinine, denatonium, cycloheximide, sucrose octaacetate, and propylthiouracil. Pairs of arrowheads of the same color along the base of each dendrogram highlight neurons that were recorded from one mouse and showed differential sensitivity to bitter stimuli (e.g., cells marked by green arrowheads were recorded from one mouse; pair in black from another, etc.). Orange arrowheads along the base of the dendrogram in panel <b>B</b> denote response data from five neurons recorded in series from one C3.SW mouse. Numbers on dendrograms mark neural clusters determined by “scree” plots. <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0041597#pone-0041597-t001" target="_blank">Table 1</a> gives stimulus abbreviations. Numbers above abbreviations for bitter stimuli indicate concentrations from lowest (e.g., 1) to highest (e.g., 5), as in <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0041597#pone-0041597-t001" target="_blank">Table 1</a>. Plots of average activity in each cluster are given below dendrograms; numbers color-matched to each plot indicate cluster(s).</p