Tension activation of mechanosensitive two-pore domain K+ channels TRAAK, TREK-1, and TREK-2.

TRAAK, TREK-1, and TREK-2 are mechanosensitive two-pore domain K+ (K2P) channels that contribute to action potential propagation, sensory transduction, and muscle contraction. While structural and functional studies have led to models that explain their mechanosensitivity, we lack a quantitative understanding of channel activation by membrane tension. Here, we define the tension response of mechanosensitive K2Ps using patch-clamp recording and imaging. All are low-threshold mechanosensitive channels (T10%/50% 0.6-2.7 / 4.4-6.4 mN/m) with distinct response profiles. TRAAK is most sensitive, TREK-1 intermediate, and TREK-2 least sensitive. TRAAK and TREK-1 are activated broadly over a range encompassing nearly all physiologically relevant tensions. TREK-2, in contrast, activates over a narrower range like mechanosensitive channels Piezo1, MscS, and MscL. We further show that low-frequency, low-intensity focused ultrasound increases membrane tension to activate TRAAK and MscS. This work provides insight into tension gating of mechanosensitive K2Ps relevant to understanding their physiological roles and potential applications for ultrasonic neuromodulation.

Plasma Levels of Interferon Gamma associated with Hearing Loss and Hearing Loss Sensation through the Handicap Questionnaire Inventory for the Elderly Screening Version.

OBJECTIVE: The aim of this study was to verify the association between the auditory handicap found in the Hearing Handicap Inventory for the Elderly-Screening Version (HHIE-S) questionnaire and hearing loss and the plasma levels of inflammatory biomarkers. MATERIALS AND METHODS: Cross-sectional study with 76 participants, 67 (88%) females and 9 (12%) males, with a mean age of 70 years. Tonal threshold audiometry and self-assessment with HHIE-S questionnaire were performed to measure the plasma levels of interleukin-2 (IL-2), IL-4, IL-6, and IL-10; tumor necrosis factor alpha; and interferon gamma (IFN-γ) flow cytometry method. For all data analyzed, the significance level adopted was P < 0.05 and 95% confidence interval. RESULTS: An inverse correlation was observed between the increase in plasma levels of IFN-γ and normal auditory handicap (P = 0.015; rs = -0.280). The severe handicap group showed an increase in the averages I (P = 0.005; rs = 0.350) and II (P = 0.016; rs = 0.368) in the right ear and the light/moderate handicap group increased the means I (P = 0.027; rs = 0.350) and II (P = 0.046; rs = 0.310) of the left ear. A statistically significant association was found between the speech recognition threshold (SRT) test results of the right ear and the severe handicap group (P = 0.002; rs = 0.271). CONCLUSIONS: There was an association between the increase in plasma levels of IFN-γ and normal auditory handicap. Additionally, statistically significant associations were observed between the mild/moderate and severe handicap groups with the increase in hearing means and an increase in SRT associated with the severe handicap group.

Gross, organoleptic and histologic assessment of cadaveric equine heads preserved using chemical methods for veterinary surgical teaching.

BACKGROUND: Preservation of biological tissues has been used since ancient times. Regardless of the method employed, tissue preservation is thought to be a vital step in veterinary surgery teaching and learning. OBJECTIVES: This study was designed to determine the usability of chemically preserved cadaveric equine heads for surgical teaching in veterinary medicine. METHODS: Six cadaveric equine heads were collected immediately after death or euthanasia and frozen until fixation. Fixation was achieved by using a hypertonic solution consisting of sodium chloride, sodium nitrite and sodium nitrate, and an alcoholic solution containing ethanol and glycerin. Chemically preserved specimens were stored at low temperatures (2°C to 6°C) in a conventional refrigerator. The specimens were submitted to gross and organoleptic assessment right after fixative solution injection (D0) and within 10, 20, and 30 days of fixation (D10, D20, and D30, respectively). Samples of tissue from skin, tongue, oral vestibule, and masseter muscle were collected for histological evaluation at the same time points. RESULTS: Physical and organoleptic assessments revealed excellent specimen quality (mean scores higher than 4 on a 5-point scale) in most cases. In some specimens, lower scores (3) were assigned to the range of mouth opening, particularly on D0 and D10. A reduced the range of mouth opening may be a limiting factor in teaching activities involving structures located in the oral cavity. CONCLUSIONS: The excellent physical, histologic, and organoleptic characteristics of the specimens in this sample support their usability in teaching within the time frame considered. Appropriate physical and organoleptic characteristics (color, texture, odor, and flexibility) of the specimens in this study support the use of the method described for preparation of reusable anatomical specimens.

An Evolving Landscape: Return of Breast Sensation After Mastectomy Varies by Anatomic Region and Reconstructive Method.

PURPOSE: Loss of breast sensation after mastectomy has been well documented. Postoperative reinnervation of the breast is influenced by factors including reconstructive technique, patient comorbidities, and adjuvant treatment. However, little attention has been paid to the differences in sensation across regions of the breast and the impact of reconstructive method on these regional differences over time. METHODS: Patients undergoing nipple-sparing mastectomy with immediate autologous or alloplastic reconstruction were prospectively followed. Neurosensory testing was performed in 9 breast regions using a pressure-specified sensory device. Patients were stratified by reconstructive technique, and regional sensation was compared at different preoperative and postoperative time points using Student t tests. RESULTS: One hundred ninety-two patients were included; 106 underwent autologous reconstruction via neurotized deep inferior epigastric artery perforator flap, and 86 underwent 2-stage alloplastic reconstruction. Preoperative sensation thresholds did not differ between reconstructive cohorts in any region and averaged 18.1 g/mm2. In the first year after mastectomy, decreased sensation was most pronounced in the inner breast regions and at the nipple areolar complex (NAC) in both reconstructive cohorts. At 4 years postoperatively, sensation increased the most at the NAC in the alloplastic cohort (34.0 g/mm2 decrease) and at the outer lateral region in the autologous cohort (30.4 g/mm2 threshold decrease). The autologous cohort experienced improved sensation compared with the alloplastic cohort in 5 of 9 regions at 1 year postoperatively, and in 7 of 9 regions at 4 years postoperatively; notably, only sensation at the outer superior and outer medial regions did not differ significantly between cohorts at 4 years postoperatively. CONCLUSIONS: Although patients undergoing breast reconstruction experience increased breast sensation over time, the return of sensation is influenced by type of reconstruction and anatomic region. Regions closer to and at the NAC experience the greatest loss of sensation after mastectomy, although the NAC itself undergoes the most sensation recovery of any breast region in those with alloplastic reconstruction.Autologous reconstruction via a neurotized deep inferior epigastric artery perforator flap results in increased return of sensation compared with alloplastic reconstruction, particularly in the inferior and lateral quadrants of the breast.

Navigation by magnetic signatures in a realistic model of Earth's magnetic field.

Certain animal species use the Earth's magnetic field (i.e. magnetoreception) alongside their other sensory modalities to navigate long distances that include continents and oceans. It is hypothesized that several animals use geomagnetic parameters, such as field intensity and inclination, to recognize specific locations or regions, potentially enabling migration without a pre-surveyed map. However, it is unknown how animals use geomagnetic information to generate guidance commands, or where in the world this type of strategy would maximize an animal's fitness. While animal experiments have been invaluable in advancing this area, the phenomenon is difficult to studyin vivoorin situ, especially on the global scale where the spatial layout of the geomagnetic field is not constant. Alongside empirical animal experiments, mathematical modeling and simulation are complementary tools that can be used to investigate animal navigation on a global scale, providing insights that can be informative across a number of species. In this study, we present a model in which a simulated animal (i.e. agent) navigates via an algorithm which determines travel heading based on local and goal magnetic signatures (here, combinations of geomagnetic intensity and inclination) in a realistic model of Earth's magnetic field. By varying parameters of the navigation algorithm, different regions of the world can be made more or less reliable to navigate. We present a mathematical analysis of the system. Our results show that certain regions can be navigated effectively using this strategy when these parameters are properly tuned, while other regions may require more complex navigational strategies. In a real animal, parameters such as these could be tuned by evolution for successful navigation in the animal's natural range. These results could also help with developing engineered navigation systems that are less reliant on satellite-based methods.

Circuit formation and sensory perception in the mouse olfactory system.

In the mouse olfactory system, odor information is converted to a topographic map of activated glomeruli in the olfactory bulb (OB). Although the arrangement of glomeruli is genetically determined, the glomerular structure is plastic and can be modified by environmental stimuli. If the pups are exposed to a particular odorant, responding glomeruli become larger recruiting the dendrites of connecting projection neurons and interneurons. This imprinting not only increases the sensitivity to the exposed odor, but also imposes the positive quality on imprinted memory. External odor information represented as an odor map in the OB is transmitted to the olfactory cortex (OC) and amygdala for decision making to elicit emotional and behavioral outputs using two distinct neural pathways, innate and learned. Innate olfactory circuits start to work right after birth, whereas learned circuits become functional later on. In this paper, the recent progress will be summarized in the study of olfactory circuit formation and odor perception in mice. We will also propose new hypotheses on the timing and gating of olfactory circuit activity in relation to the respiration cycle.

Shared structure of fundamental human experience revealed by polysemy network of basic vocabularies across languages.

How are concepts related to fundamental human experiences organized within the human mind? Our insights are drawn from a semantic network created using the Cross-Linguistic Database of Polysemous Basic Vocabulary, which focuses on a broad range of senses extracted from dictionary entries. The database covers 60 basic vocabularies in 61 languages, providing 11,841 senses from 3736 entries, revealing cross-linguistic semantic connections through automatically generated weighted semantic maps. The network comprises 2941 nodes connected by 3573 edges. The nodes representing body parts, motions, and features closely related to human experience occupy wide fields or serve as crucial bridges across semantic domains in the network. The polysemous network of basic vocabularies across languages represents a shared cognitive network of fundamental human experiences, as these semantic connections should be conceived as generally independent of any specific language and are driven by universal characteristics of the real world as perceived by the human mind. The database holds the potential to contribute to research aimed at unraveling the nature of cognitive proximity.

Human sensory adaptation to the ecological structure of environmental statistics.

Humans acquire sensory information via fast, highly specialized detectors: For example, edge detectors monitor restricted regions of visual space over timescales of 100-200 ms. Surprisingly, this study demonstrates that their operation is nevertheless shaped by the ecological consistency of slow global statistical structure in the environment. In the experiments, humans acquired feature information from brief localized elements embedded within a virtual environment. Cast shadows are important for determining the appearance and layout of the environment. When the statistical reliability of shadows was manipulated, human feature detectors implicitly adapted to these changes over minutes, adjusting their response properties to emphasize either "image-based" or "object-based" anchoring of local visual elements. More specifically, local visual operators were more firmly anchored around object representations when shadows were reliable. As shadow reliability was reduced, visual operators disengaged from objects and became anchored around image features. These results indicate that the notion of sensory adaptation must be reframed around complex statistical constructs with ecological validity. These constructs far exceed the spatiotemporal selectivity bandwidth of sensory detectors, thus demonstrating the highly integrated nature of sensory processing during natural behavior.

Influence of taste sensitivity on preference and sensory perception of mezcal.

The perception of orosensory stimuli, which includes flavor, can vary between individuals. These individual variations in oral sensations can be due to genetic factors and it would appear that they can predict food liking and consumption. The most studied source of variation is related to bitter taste perception associated with 6-n-propylthiouracil (PROP) responsiveness. In this context, humans can be classified as non-tasters (NT), medium tasters (MT) and supertasters (ST). Evidence suggests that genetic variation in bitter taste perception contributes to differences in the level of irritation caused by alcohol perception in solutions. The aim of this investigation was to study the bitter taste sensitivity among a group of mezcal consumers and its relationship with sensory perception and preference through PROP taster status. The tests were carried out in the state of Oaxaca in Mexico. A total of 83 mezcal consumers were classified by their PROP taster status and were asked to provide sensory descriptors for five mezcal samples and rate them according to the level of liking. The three-solution test was used to classify the subjects as NT, MT, and ST, while a Multiple Factor Analysis (MFA) was used to visualize the sensory descriptors provided by these three groups. The proportion of MT subjects was 16%, while the proportion of NT and ST was 34 and 51%, respectively. The MT provided higher liking ratings for at least three mezcal samples. According to MFA, the mezcal samples were organized in a similar configuration along the two dimensions. However, NT mentioned a limited number of simple terms (strong flavor, tasteless, burning in the mouth) to describe the samples, whereas ST used a more complex vocabulary (astringent, smoky, scratchy aftertaste). These data suggest that the preference for mezcal samples was similar for non-taster and supertasters, but there are indications that the sensory perception of mezcal differs between groups.

An insular cortical circuit required for itch sensation and aversion.

Itch encompasses both sensory and emotional dimensions, with the two dimensions reciprocally exacerbating each other. However, whether a shared neural circuit mechanism governs both dimensions remains elusive. Here, we report that the anterior insular cortex (AIC) is activated by both histamine-dependent and -independent itch stimuli. The activation of AIC elicits aversive emotion and exacerbates pruritogen-induced itch sensation and aversion. Mechanistically, AIC excitatory neurons project to the GABAergic neurons in the dorsal bed nucleus of the stria terminalis (dBNST). Manipulating the activity of the AIC → dBNST pathway affects both itch sensation and itch-induced aversion. Our study discovers the shared neural circuit (AIC â†’ dBNST pathway) underlying the itch sensation and aversion, highlights the critical role of the AIC as a central hub for the itch processing, and provides a framework to understand the neural mechanisms underlying the sensation and emotion interaction.

Saccades to partially occluded objects: Perceptual completion mediates oculomotor control.

Oculomotor behavior typically consists of directing gaze to objects in complex scenes for the purpose of extracting detailed perceptual information. Here, we probed the nature of the visual representations over which saccades to objects are computed. We contrasted an image-based oculomotor control hypothesis, holding that saccades are computed solely over information explicit in the retinal image, and an object-based oculomotor control hypothesis, holding that saccades are computed over object representations reflecting the three-dimensional structure of the scene. We recorded saccade landing positions to partially occluded objects in a naturalistic search task. In Experiment 1, saccade landing positions were biased toward the center of the perceptually completed object. Experiment 2 demonstrated that the bias held even when it would have been strategically advantageous to avoid it. Experiment 3 demonstrated that the bias was not due to image-level differences generated by the presence of occluders. The results indicate that saccade motor programs are computed, at least in part, over object-level representations reflecting the completion of occluded surfaces.

Binocular luster elicited by isoluminant chromatic stimuli relies on mechanisms similar to those in the achromatic case.

The phenomenon of binocular luster can be evoked by simple dichoptic center-surround stimuli showing a luminance contrast difference between the eyes. Previous findings support the idea that this phenomenon is mediated by a low-level conflict mechanism that integrates the monocular signals from different types of contrast detector cells. Also, isoluminant stimuli with different chromatic contrasts between eyes can trigger sensations of luster. Here, we investigate whether the lustrous impression in such purely chromatic stimuli depends on interocular contrast differences and in particular on interocular contrast polarity pairings in a similar way as in the achromatic case. In our experiments, we measured the magnitude of the lustrous response using a series of isoluminant dichoptic center-ring-surround stimuli with varying ring width whose chromatic properties were varied along the red-green and blue-yellow cardinal directions. The trends in the data were very similar to those of our former study with achromatic stimuli, indicating similar mechanisms in both cases. The empirical luster data could also be predicted fairly well by a chromatic version of our interocular conflict model (with overall R2 values between 0.577 and 0.639), for which two different receptive field models were used, simulating the behavior of color-sensitive double-opponent cells in V1.

Sensory neurobiology: Muscles power pheromone sensation.

While we understand how the five main sensory organs enable and facilitate stimulus detection, little is known about how the vomeronasal organ enables pheromone sensation. A new study finds specialized muscles poised to coordinate stimulus delivery, dynamics, and arousal.

Patient-Reported Outcomes on Subjective Nipple Sensation After Double-Incision and Periareolar Mastectomy for Chest Masculinization: Subjective Nipple Sensation After Chest Masculinization.

ABSTRACT: We evaluated patient-reported outcomes to assess for patient and procedural factors associated with postchest masculinization subjective nipple sensation. Patients who underwent double-incision or periareolar mastectomies for chest masculinization by a single senior surgeon (2015-2019) were surveyed at 2 time points regarding postoperative nipple sensation and satisfaction, including patient-reported outcomes using BODY-Q modules (Q-Portfolio.org). Demographic, operative, and postoperative variables were obtained from medical records. Patients were stratified according to survey responses. Univariate and multivariate analyses were performed.Response rate was 42% for survey 1 and 22% for survey 2. Of the 151 survey 1 responders, 138 (91.4%) received double-incision mastectomies and 13 (8.6%) received periareolar mastectomies. Among Survey 1 responders, 84.6% periareolar patients and 69.6% double-incision patients reported "completely" or "a little" nipple sensation preservation, and the difference trended toward significance (P = 0.0719). There was a stepwise increase in proportion of patients reporting sensation with greater recovery time until response to survey 1. Obesity (P = 0.0080) and greater tissue removed (P = 0.0247) were significantly associated with decreased nipple sensation. Nipple satisfaction scores were significantly higher for patients reporting improved nipple sensation (P = 0.0235). Responders to survey 2 who reported greater satisfaction with nipple sensation were significantly more likely to report preserved sensitivity to light touch (P = 0.0277), pressure (P = 0.0046), and temperature (P = 0.0031). Preserved erogenous sensation was also significantly associated with greater satisfaction (P = 0.0018).In conclusion, we found that nipple sensation may be associated with postoperative nipple satisfaction. Operative techniques to optimize nipple sensation preservation may improve this population's postoperative satisfaction.

Effect of modifying pumpkin preparation on oral processing of breads.

There is an increasing demand for texture sensations of bread during mastication, with reformulation being needed. This study investigated how bread structure influences oral processing behavior and texture perception. Variations in bread structure were created by manipulating ingredient additions, including pumpkin content and pumpkin processing methods. Results indicated that the physical, chemical, and structural properties drove the oral processing behaviors, and texture sensations were highly correlated with bolus properties. At the beginning and middle of the mastication, bolus from breads with low pumpkin-content required more saliva and exhibited greater hardness, lower adhesiveness, and a higher proportion of small-piece particles than the bolus from high pumpkin-content breads. Bolus from pumpkin pulp breads required more saliva, and was softer, stickier, and generated particles with a lower degree of degradation than the bolus from pumpkin puree breads. However, at the end period, the bolus properties tended to change to similar values. Low pumpkin content breads were initially perceived chewy, whereas high pumpkin content, soft. The dominance rate for soft sensation was higher and lasted longer in breads with pumpkin puree than in breads with pumpkin pulp. Finally, six bread samples were all perceived as hydrated, sticky, and crumbly. This study contributes to a better understanding of the impact of reformulation on oral behavior and sensory properties.

Taste dysfunction as a predictor of depression in schizophrenia: A systematic review and meta-analysis.

OBJECTIVE: This study aims to investigate the relationship between taste dysfunction and depression among patients with schizophrenia, to achieve early detection of depression in clinical practice. METHODS: Following PRISMA guidance, a comprehensive literature search was conducted globally, covering papers published from 1961 to June 2023. A total of 17 manuscripts were selected through meta-analysis and sensitivity analysis after examining available materials from seven databases to determine the correlation between depression and taste dysfunction. RESULTS: The comparison of the 17 selected manuscripts revealed that individuals with gustatory dysfunction may be more likely to experience depressive symptoms (SMD, 0.51, 95% CI, 0.08 to 0.93, p = 0.02). Depression is associated with taste dysfunction in certain aspects, as indicated by the pleasantness ratings of sucrose solutions (SMD, -0.53, 95% confidence interval [CI] -1.11 to 0.05, p = 0.08), gustatory identification ability (SMD, 0.96, 95% CI, 0.03 to 1.89, p = 0.04), and the perception threshold of sweet taste (MD, 0.80, 95% CI, 0.79 to 0.81, p < 0.00001). CONCLUSIONS: Due to variations in the methods, designs, and selection criteria employed in the included studies, it is necessary to establish a feasible framework. Future research using detailed and targeted approaches can provide clearer and more unified conclusions on the relationship between taste dysfunction and depression. Moreover, further high-quality research is needed to obtain clearer conclusions and explore the potential of taste dysfunction as an effective tool for early screening of depression. TRIAL REGISTRATION: This review has been registered in the PROSPERO on April 2022 with the identifier CRD42023400172.

Modeling circuit mechanisms of opposing cortical responses to visual flow perturbations.

In an ever-changing visual world, animals' survival depends on their ability to perceive and respond to rapidly changing motion cues. The primary visual cortex (V1) is at the forefront of this sensory processing, orchestrating neural responses to perturbations in visual flow. However, the underlying neural mechanisms that lead to distinct cortical responses to such perturbations remain enigmatic. In this study, our objective was to uncover the neural dynamics that govern V1 neurons' responses to visual flow perturbations using a biologically realistic computational model. By subjecting the model to sudden changes in visual input, we observed opposing cortical responses in excitatory layer 2/3 (L2/3) neurons, namely, depolarizing and hyperpolarizing responses. We found that this segregation was primarily driven by the competition between external visual input and recurrent inhibition, particularly within L2/3 and L4. This division was not observed in excitatory L5/6 neurons, suggesting a more prominent role for inhibitory mechanisms in the visual processing of the upper cortical layers. Our findings share similarities with recent experimental studies focusing on the opposing influence of top-down and bottom-up inputs in the mouse primary visual cortex during visual flow perturbations.

Information-Theoretical Analysis of the Cycle of Creation of Knowledge and Meaning in Brains under Multiple Cognitive Modalities.

It is of great interest to develop advanced sensory technologies allowing non-invasive monitoring of neural correlates of cognitive processing in people performing everyday tasks. A lot of progress has been reported in recent years in this research area using scalp EEG arrays, but the high level of noise in the electrode signals poses a lot of challenges. This study presents results of detailed statistical analysis of experimental data on the cycle of creation of knowledge and meaning in human brains under multiple cognitive modalities. We measure brain dynamics using a HydroCel Geodesic Sensor Net, 128-electrode dense-array electroencephalography (EEG). We compute a pragmatic information (PI) index derived from analytic amplitude and phase, by Hilbert transforming the EEG signals of 20 participants in six modalities, which combine various audiovisual stimuli, leading to different mental states, including relaxed and cognitively engaged conditions. We derive several relevant measures to classify different brain states based on the PI indices. We demonstrate significant differences between engaged brain states that require sensory information processing to create meaning and knowledge for intentional action, and relaxed-meditative brain states with less demand on psychophysiological resources. We also point out that different kinds of meanings may lead to different brain dynamics and behavioral responses.