A vagal reflex evoked by airway closure.

Airway integrity must be continuously maintained throughout life. Sensory neurons guard against airway obstruction and, on a moment-by-moment basis, enact vital reflexes to maintain respiratory function1,2. Decreased lung capacity is common and life-threatening across many respiratory diseases, and lung collapse can be acutely evoked by chest wall trauma, pneumothorax or airway compression. Here we characterize a neuronal reflex of the vagus nerve evoked by airway closure that leads to gasping. In vivo vagal ganglion imaging revealed dedicated sensory neurons that detect airway compression but not airway stretch. Vagal neurons expressing PVALB mediate airway closure responses and innervate clusters of lung epithelial cells called neuroepithelial bodies (NEBs). Stimulating NEBs or vagal PVALB neurons evoked gasping in the absence of airway threats, whereas ablating NEBs or vagal PVALB neurons eliminated gasping in response to airway closure. Single-cell RNA sequencing revealed that NEBs uniformly express the mechanoreceptor PIEZO2, and targeted knockout of Piezo2 in NEBs eliminated responses to airway closure. NEBs were dispensable for the Hering-Breuer inspiratory reflex, which indicated that discrete terminal structures detect airway closure and inflation. Similar to the involvement of Merkel cells in touch sensation3,4, NEBs are PIEZO2-expressing epithelial cells and, moreover, are crucial for an aspect of lung mechanosensation. These findings expand our understanding of neuronal diversity in the airways and reveal a dedicated vagal pathway that detects airway closure to help preserve respiratory function.

Appraisal of Burden of Caregivers to Chronically Rehabilitated Patients with Spinal Cord Injuries in a Tertiary Neurological Center in Nepal.

The care of a patient with a spinal cord injury is part of healthcare systems. It causes a substantial physical and emotional drain on the caretakers who often are in short supply and thus may lack adequate training, preparation, and support. Long hours of assisting a chronically handicapped patient with activities of daily living and exercises decrease the rehabilitator's quality of life and take a psychological toll that increases a risk of burnout syndrome. The present study found a significant caregiving burden among care providers of chronically dependent patients with spinal cord injuries. Additionally, financial drain escalates the issue in this rather neglected health and quality of life aspect concerning caregivers. For the situation to improve, there must be a paradigm shift in care taking toward the motivative patient's participation in the rehabilitative process. Provisions for social support and educational programs focusing on the patients and their families need to be reappraised.

Comparative prospective study between medial and lateral distal tibial locking compression plates for distal third tibial fractures.

PURPOSE: Tibial fracture is the most common long bone fracture. Distal third tibial fractures are challenging though open reduction and plating can result in anatomical reduction and rigid fixation. This paper aimed to evaluate and compare the results of medial and lateral locking compression plates for distal third tibial fractures. METHODS: This prospective clinical study involved 36 patients with distal tibial fractures admitted in Department of Orthopaedics, Sawai Mansingh Medical College & Affiliated Hospital, Jaipur, India, from June 2011 to May 2012, including 29 closed fractures and 7 open fractures at the mean age of 38.9 years. Thirty-six patients were divided equally into two groups based on treatment method, including medial plating group (18 patients) and lateral plating group (18 patients). They were followed up for at least 5 months after discharge. The functional outcomes were evaluated using Tenny and Wiss clinical assessment criteria. RESULTS: Malunion was found in 3 cases of medial plating group and in 1 case of lateral plating group. In the medial plating group, there were 5 cases of superficial infections, 1 deep infection, 1 nonunion and 3 wound dehiscence. In the lateral plating group, there was 1 case of superficial infections, 1 deep infection and 1 nonunion. In the lateral plating group, 4 patients reported feeling the plates and screws but none of them asked to remove the hardware. In the medial plating group, 9 patients reported symptomatic hardware problems and 7 asked to remove the hardware. The number of cases graded as excellent/good/fair was 1/8/7 in the medial plating group and 3/7/7 in the lateral plating group respectively. In the medial plating group, the final range of motion was 17.2° in ankle dorsiflexion and 30.7° in ankle plantar flexion. In the lateral plating group, the final range of motion was 19° in ankle dorsiflexion and 34.2° in ankle plantar flexion. CONCLUSION: Lateral plating of distal tibia is safe and feasible, which can provide biological fixation and prevent the soft tissue complications associated with medial plating.

A bony foreign body found in a patient with no bony injury: a case report.

Open fractures with bone loss are a common occurrence following high energy trauma. But usually the bone fragments are lost on the roadside and are not usable. We report a patient who was involved in a head-on collision between two wheelers and presented with a bone fragment embedded in his thigh. Radiological survey revealed no bony injury in that patient. Another patient, who presented at the same time, sustained a segmental fracture of shaft femur and was found to have lost a bone fragment that was similar to the one found in previous patient. CT scan with 3D reconstruction revealed this missing fragment to be the same as that found in previous patient. Both patients had a history of head-on collision while travelling on a two-wheeler. Present case report throws some highlights on the probable mechanism of injury.

Combining supervised and unsupervised analyses to quantify behavioral phenotypes and validate therapeutic efficacy in a triple transgenic mouse model of Alzheimer's disease.

Behavioral testing is an essential tool for evaluating cognitive function and dysfunction in preclinical research models. This is of special importance in the study of neurological disorders such as Alzheimer's disease. However, the reproducibility of classic behavioral assays is frequently compromised by interstudy variation, leading to ambiguous conclusions about the behavioral markers characterizing the disease. Here, we identify age- and genotype-driven differences between 3xTg-AD and non-transgenic control mice using a low-cost, highly customizable behavioral assay that requires little human intervention. Through behavioral phenotyping combining both supervised and unsupervised behavioral classification methods, we are able to validate the preventative effects of the immunosuppressant cyclosporine A in a rodent model of Alzheimer's disease, as well as the partially ameliorating effects of candidate drugs nebivolol and cabozantinib.

Changing neuroestrogens within the auditory forebrain rapidly transform stimulus selectivity in a downstream sensorimotor nucleus.

The activity of sensory circuits is shaped by neuromodulators, which can have downstream consequences for both sensorimotor integration and behavioral output. Recent evidence indicates that brain-derived estrogens ("neuroestrogens") can act as local circuit modulators in the songbird auditory forebrain. Specifically, neuroestrogens fluctuate in the auditory caudomedial nidopallium (NCM) during social interactions and in response to song stimuli. Within minutes of elevation, neuroestrogens also enhance auditory response properties of NCM neurons, and acute blockade of estrogen production in NCM disrupts behavioral song preferences. Here, we test the hypothesis that fluctuating neuroestrogens within NCM influence stimulus selectivity in a downstream sensorimotor nucleus (HVC, used as a proper name) that receives indirect auditory input from NCM. Dual extracellular recordings coupled with retrodialysis delivery show that song selectivity in HVC is rapidly enhanced by increasing neuroestrogens in NCM in adult males. Conversely, inhibiting neuroestrogen production in NCM causes a rapid decline in song selectivity in HVC, demonstrating the endogenous nature of this modulatory network. In contrast, HVC selectivity is unaffected by neuroestrogen delivery to either nearby caudomedial mesopallium or into HVC itself, indicating that neuroestrogen actions are restricted to NCM. In juvenile males, identical neuroestrogen treatment in NCM also does not alter HVC selectivity, consistent with a developmental maturation of the auditory network. Lastly, the rapid actions of estrogens leading to enhanced HVC selectivity appear to be mediated by membrane-bound receptors in NCM. These findings indicate that steroid-dependent modulation of sensory processing is not locally restricted and can be transmitted transynaptically to influence downstream sensorimotor and premotor targets.

Interplay between biochemical processes and network properties generates neuronal up and down states at the tripartite synapse.

Neuronal up and down states have long been known to exist both in vitro and in vivo. A variety of functions and mechanisms have been proposed for their generation, but there has not been a clear connection between the functions and mechanisms. We explore the potential contribution of cellular-level biochemistry to the network-level mechanisms thought to underlie the generation of up and down states. We develop a neurochemical model of a single tripartite synapse, assumed to be within a network of similar tripartite synapses, to investigate possible function-mechanism links for the appearance of up and down states. We characterize the behavior of our model in different regions of parameter space and show that resource limitation at the tripartite synapse affects its ability to faithfully transmit input signals, leading to extinction-down states. Recovery of resources allows for "reignition" into up states. The tripartite synapse exhibits distinctive "regimes" of operation depending on whether ATP, neurotransmitter (glutamate), both, or neither, is limiting. Our model qualitatively matches the behavior of six disparate experimental systems, including both in vitro and in vivo models, without changing any model parameters except those related to the experimental conditions. We also explore the effects of varying different critical parameters within the model. Here we show that availability of energy, represented by ATP, and glutamate for neurotransmission at the cellular level are intimately related, and are capable of promoting state transitions at the network level as ignition and extinction phenomena. Our model is complementary to existing models of neuronal up and down states in that it focuses on cellular-level dynamics while still retaining essential network-level processes. Our model predicts the existence of a "final common pathway" of behavior at the tripartite synapse arising from scarcity of resources and may explain use dependence in the phenomenon of "local sleep." Ultimately, sleeplike behavior may be a fundamental property of networks of tripartite synapses.

An 8-cage imaging system for automated analyses of mouse behavior.

The analysis of mouse behavior is used in biomedical research to study brain function in health and disease. Well-established rapid assays allow for high-throughput analyses of behavior but have several drawbacks, including measurements of daytime behaviors in nocturnal animals, effects of animal handling, and the lack of an acclimation period in the testing apparatus. We developed a novel 8-cage imaging system, with animated visual stimuli, for automated analyses of mouse behavior in 22-h overnight recordings. Software for image analysis was developed in two open-source programs, ImageJ and DeepLabCut. The imaging system was tested using 4-5 month-old female wild-type mice and 3xTg-AD mice, a widely-used model to study Alzheimer's disease (AD). The overnight recordings provided measurements of multiple behaviors including acclimation to the novel cage environment, day and nighttime activity, stretch-attend postures, location in various cage areas, and habituation to animated visual stimuli. The behavioral profiles were different in wild-type and 3xTg-AD mice. AD-model mice displayed reduced acclimation to the novel cage environment, were hyperactive during the first hour of darkness, and spent less time at home in comparison to wild-type mice. We propose that the imaging system may be used to study various neurological and neurodegenerative disorders, including Alzheimer's disease.

Outcomes of Osteoid Osteoma Treated by Percutaneous CT-Guided Radiofrequency Ablation.

Introduction Osteoid osteomas are the most frequent true benign bone tumor in the adolescent age group and the third most prevalent benign bone tumor overall. This study was designed to assess the effectiveness of the procedure and correlate it with the analgesia offered because of the significant burden of this illness and new literature supporting the successful outcomes of image-guided percutaneous radiofrequency ablation (RFA) in osteoid osteoma. Methodology  This hospital-based interventional trial was carried out in a tertiary care referral center. Forty-two patients with osteoid osteoma, ranging in age from 9 to 30, were included in the study. The patients received RFA guided by computed tomography (CT), and they were postoperatively monitored at one, two, and four weeks and three, six months, and 12 months. A numerical pain scale (NPS) was used to evaluate the patient's pain both before and after the procedure. The preoperative and postoperative results were contrasted. Results A total of 42 participants were enrolled in the study. Eight (19.05%) women and 34 (80.95%) men made up the group. Complete pain alleviation (NPS=0) was attained in 42.8% and 96.4% of the study group in the first and second weeks post-procedure. Almost all patients began protected weight-bearing at one week, according to their level of pain tolerance. Osteoid osteoma of the talus was a remnant lesion in one patient that required further treatment after two weeks. During the duration of the follow-up, no problems were recorded. Conclusion Percutaneous CT-guided RFA of osteoid osteoma is a safe, minimally invasive procedure and greatly reduces the duration of hospitalization. It has excellent functional outcomes and no known complications.

Enteroendocrine cell lineages that differentially control feeding and gut motility.

Enteroendocrine cells are specialized sensory cells of the gut-brain axis that are sparsely distributed along the intestinal epithelium. The functions of enteroendocrine cells have classically been inferred by the gut hormones they release. However, individual enteroendocrine cells typically produce multiple, sometimes apparently opposing, gut hormones in combination, and some gut hormones are also produced elsewhere in the body. Here, we developed approaches involving intersectional genetics to enable selective access to enteroendocrine cells in vivo in mice. We targeted FlpO expression to the endogenous Villin1 locus (in Vil1-p2a-FlpO knock-in mice) to restrict reporter expression to intestinal epithelium. Combined use of Cre and Flp alleles effectively targeted major transcriptome-defined enteroendocrine cell lineages that produce serotonin, glucagon-like peptide 1, cholecystokinin, somatostatin, or glucose-dependent insulinotropic polypeptide. Chemogenetic activation of different enteroendocrine cell types variably impacted feeding behavior and gut motility. Defining the physiological roles of different enteroendocrine cell types provides an essential framework for understanding sensory biology of the intestine.

In silico analysis of peptide binding features of HLA-B*4006.

HLA-B*4006 is the most common allele amongst Indians. It belongs to the 'HLA-B44 supertype' family of alleles that constitute an important component of the peptide binding repertoire in populations world over. Its peptide binding characteristics remain poorly examined. The amino acid sequence and structural considerations suggest a small, poorly hydrophobic 'F' pocket for this allele that may adversely affect the interaction with the C terminal residue of the antigenic peptide. Contribution of auxiliary anchor residues (P3) of the peptide has also been indicated. To examine these aspects by in silico analysis, HLA-B*4001, 4002, and 4006 alleles were modeled using HLA-B*4402 as a template. Eleven peptides, known to bind alleles of this family, were used for docking and molecular dynamics studies. Interaction between the amino group (main-chain) of P3 residue and Tyr99 of the alleles was seen in majority of peptide-complexes. Hydrophobic interactions between Tyr7 and Tyr159 with N terminal residues of the peptide were also seen in all the complexes. Replacement of Trp95 by leucine in HLA-B*4006 resulted in reduction of binding free energy in 8 out of 9 complexes. In summary, the analysis of the modeled structures and HLA-peptide complexes strongly supports the adverse effect of Trp95 at pocket F and the possible role of the third residue of the antigenic peptide as an auxiliary anchor in HLA-B*4006 peptide complexes. In the light of suggested promiscuous peptide binding pattern and association with risk for tuberculosis/HIV for this allele, the ascertainment of the predicted effects of Trp95 and role of P3 residue as an auxiliary anchor by this preliminary in silico analysis thus helps define direction of the further studies.

Functional outcome of ankle fracture patients treated with biodegradable implants.

BACKGROUND: Biodegradable devices have been developed to overcome the disadvantages of metallic implants especially the need for their subsequent removal, though they have their own drawbacks like poor mechanical properties and tissue reactions. Aim of this prospective study was to access the outcome of bimalleolar fractures fixed with biodegradable plates and screws. METHODS: A prospective study was conducted between July 2006 and November 2008 comprising of sixteen patients with unilateral bimalleolar fractures. Fibula fractures were fixed with biodegradable plates and medial malleoli with screws. Patients were followed at two weeks, six weeks, three months, six months, twelve months and eighteen months. Final evaluation was done using Olerud Molander ankle score. RESULTS: Six patients had excellent results; four patients had good results and six patients had fair performance. No patient in this series had a poor outcome. One patient had both pain and swelling at 14 weeks postoperatively which settled down with debridement and antibiotics. None of the patients needed implant removal. CONCLUSION: Biodegradable plates and screws when used to fix bimalleolar fracture along with restricted weight bearing, provide satisfactory fracture healing, good functional results and reduce the need of implant removal.

Ilizarov hip reconstruction in skeletally mature young patients with chronic unstable hip joints.

PURPOSE: Hip reconstruction with subtrochanteric valgus extension pelvic support osteotomy and distal femoral osteotomy for lengthening and varus correction is one of the options available for salvage of chronic unstable hips and is also known as Ilizarov hip reconstruction (IHR). This study evaluated the outcomes and complications associated with IHR in skeletally mature young patients. METHODS: Twelve patients (7 males, 5 females) with a mean age of 23 years underwent IHR for chronically dislocated hips due to various causes. Preoperative clinical and radiological evaluations were used to determine the site of osteotomies and the required angulations. Postoperatively the patients were followed up clinically and radiologically for a minimum of 36 months. Ilizarov fixator was removed when adequate lengthening was achieved and there was radiological evidence of union. Harris Hip Score was used to document hip function preoperatively and at final evaluation. RESULTS: Significant improvements occurred in limb length discrepancy (LLD) 5.11 cm preoperatively to 0.9 cm at final evaluation, Harris Hip Score 44.33 points preoperatively to 70.83 points (p < 0.0001) at final evaluation. Trendelenberg sign disappeared completely in nine patients and was delayed in three at final evaluation. The abduction at the hip increased from the preoperative mean of 12.08° (range 0°-25°) to 22.5° (range 15°-35°) postoperatively. The fixed flexion deformity at the hip decreased from 22° (range 10°-35°) preoperatively to 3° postoperatively (range 0°-10°). The amount of free flexion at the operated hips decreased from the preoperative mean of 88.33° (range 70°-120°) to 70.42° (range 45°-105°) at final follow up. The mean fixator interval was 7.33 months (5-12 months) and the mean follow up duration was 59.4 months (38-86 months). CONCLUSIONS: IHR is effective in improving the hip biomechanics, correcting the LLD and eliminating the Trendelenberg sign. Lengthy period of fixator wear, knee stiffness and pin tract infections, though minor are known limitations of this procedure.

Simultaneous asymmetrical bilateral hip dislocations - A report of three cases with different presentations and management.

BACKGROUND: Simultaneous traumatic dislocation of both the hips in an individual is an uncommon injury. It accounts for only 1-2% of all traumatic hip dislocations. Simultaneous traumatic dislocation of both the hips in opposite directions i.e., anterior dislocation of one hip and posterior of the other is even rarer. These asymmetric dislocations need prompt identification for appropriate management. While their management should proceed in a manner commensurate with the accepted management of isolated dislocations to avoid complications, it is the timely identification which is essential. STUDY DETAILS: Retrospectively the details of three patients with asymmetric bilateral hip dislocations were collected. The article describes the clinical presentation of each patient and the management offered to them. The follow up duration ranged from 15 months to 24 months. RESULTS: In the short term, the outcomes in terms of hip pain, movements at the hips and radiological parameters like absence of arthritic or avascular changes were found to be satisfactory in each patient. CONCLUSION: Early diagnosis and prompt reduction is the essential first step in the appropriate management of these patients to prevent the possible complications. The associated fractures must be managed as per the established principles of trauma care. Long term follow up is essential for identifying if complications like avascular necrosis and secondary osteoarthritis develop after this uncommon injury.

Olfactory landmarks and path integration converge to form a cognitive spatial map.

The convergence of internal path integration and external sensory landmarks generates a cognitive spatial map in the hippocampus. We studied how localized odor cues are recognized as landmarks by recording the activity of neurons in CA1 during a virtual navigation task. We found that odor cues enriched place cell representations, dramatically improving navigation. Presentation of the same odor at different locations generated distinct place cell representations. An odor cue at a proximal location enhanced the local place cell density and also led to the formation of place cells beyond the cue. This resulted in the recognition of a second, more distal odor cue as a distinct landmark, suggesting an iterative mechanism for extending spatial representations into unknown territory. Our results establish that odors can serve as landmarks, motivating a model in which path integration and odor landmarks interact sequentially and iteratively to generate cognitive spatial maps over long distances.

Anticancer and immunomodulatory activities of novel 1,8-naphthyridine derivatives.

A number of 1,8-naphthyridine derivatives (22-62) have been synthesized and screened for their in vitro cytotoxicity against eight tumors and two non-tumor cell lines. Halogen substituted 1,8-naphthyridine-3-caboxamide derivatives showed potent activity with compound 47 having IC(50) of 0.41 and 0.77 microM on MIAPaCa and K-562 cancer cell lines, respectively while, compound 36 had IC(50) of 1.19 microM on PA-1 cancer cell line. However, one of the unsubstituted 1,8-naphthyridine-C-3'-heteroaryl derivative 29 showed potent cytotoxicity with IC(50) of 0.41 and 1.4 microM on PA-1 and SW620 cancer cell lines, respectively. These compounds were also evaluated for anti-inflammatory activity as suggested by downregulation of proinflammaotory cytokines.

Unreamed Intra-Medullary Nail Versus Half Pin External Fixator in Grade III [A & B] Open tibia fractures.

BACKGROUND: Tibia fracture is the most common long bone fracture. The fractures of tibia are commonly open fractures due to subcutaneous position of the tibia. The choice of technique for stabilization of open tibia fractures includes - External fixation, unreamed intra-medullary nails [URTN], Reamed intra-medullary nails, ORIF with Plating. OBJECTIVES: To evaluate & compare the results of Unreamed Intra-Medullary Nail Versus Half Pin External Fixator in Grade III [A & B] Open tibia fractures. METHODS: This prospective clinical study [Randomized chit box] was done on 50 patients presenting to our institute within 24 h of injury. Only those who were skeletally mature with open tibia fracture Grade IIIA & IIIB [Gustilo-Anderson] were included in this study. After initial management, radiological assessment was done. Following this adequate wound debridement, skeletal stabilization with either primary URTN or external fixator was done. Inspection and debridement were repeated at 48-h intervals until the wound was considered clean. RESULTS: 50 cases [25 each group] were compared in terms of - Final Alignment of the Fracture, Presence of Infection/Non-union/Mal-union, Hardware failure, Time to Bone Union, Number of Operative Procedures after index admission. Mean time to full weight bearing was 20.96 weeks in URTN group versus 24.8 weeks in Ex-fix group. 5 in URTN group required further surgery for non-union versus 11 patients in Ex-fix group. There were 6 significant pin track infection. Removal of nail was required in 1 case of deep infection. CONCLUSION: This study supports the use of the URTN over External fixator in the treatment of severe open tibia fractures.

Primary ilizarov external fixation in open grade III type C distal femur fractures: Our experience.

INTRODUCTION: Open comminuted distal femur fractures are notorious for septic or aseptic non-union. The recommended fixed angle distal femur locking plate in such situations can lead to a septic non-union due to its extensive approach and further periosteal stripping. Supracondylar nails, though have a minimally invasive approach, are not suitable for type C2 and C3 (AO/ASIF) fractures. A monolateral fixator as damage control followed by plating may be recommended. But if wound healing is delayed it results in difficult articular reduction, poor alignment and a stiff knee. We therefore used ilizarov circular external fixators (ICEF) for such open fractures (type C1, C2 and C3) and analysed its radiological and functional outcomes. MATERIALS AND METHODS: 25 male patients, with a mean age of 31.04 ±â€¯6.62 years (range, 22-44 years), with open grade III type C distal femoral fractures were treated with ICEF. There were 7 fractures of type C1and C3 each, 11 were of type C2. Articular reduction and compression was achieved with inter-fragmentary screws through minimal open technique by extending the open wound and then stabilising the fracture with ICEF. The main outcomes evaluated were union, range of motion, final shortening, Knee Society scoring and ASAMI scoring system for radiological and functional outcomes. RESULTS: The mean follow-up period was 19.12 ±â€¯1.14 months. All fractures except two united at a mean period of 30 ±â€¯3.02 weeks, without the need of bone grafts. The bony assessment (according to ASAMI score) was excellent in 8 cases (33.33%), good in 9 cases (37.5%) and fair in 5 cases (20.83%), while there were 2 poor clinical end results. The functional results were excellent in 6 cases (25%), good in 9 cases (37.5%) fair in 6 cases (25%) poor in 3 cases (12.5%). The complications included shortening, extension lag and pin tract infections. CONCLUSION: With the encouraging results, the use of ICEF with minimal internal fixation in grade III open comminuted distal femur fractures as a primary definitive treatment is a valuable alternative.

Arterial Baroreceptors Sense Blood Pressure through Decorated Aortic Claws.

Mechanosensory neurons across physiological systems sense force using diverse terminal morphologies. Arterial baroreceptors are sensory neurons that monitor blood pressure for real-time stabilization of cardiovascular output. Various aortic sensory terminals have been described, but those that sense blood pressure are unclear because of a lack of selective genetic tools. Here, we find that all baroreceptor neurons are marked in Piezo2-ires-Cre mice and then use genetic approaches to visualize the architecture of mechanosensory endings. Cre-guided ablation of vagal and glossopharyngeal PIEZO2 neurons eliminates the baroreceptor reflex and aortic depressor nerve effects on blood pressure and heart rate. Genetic mapping reveals that PIEZO2 neurons form a distinctive mechanosensory structure: macroscopic claws that surround the aortic arch and exude fine end-net endings. Other arterial sensory neurons that form flower-spray terminals are dispensable for baroreception. Together, these findings provide structural insights into how blood pressure is sensed in the aortic vessel wall.

Cellular and Neural Responses to Sour Stimuli Require the Proton Channel Otop1.

The sense of taste allows animals to sample chemicals in the environment prior to ingestion. Of the five basic tastes, sour, the taste of acids, had remained among the most mysterious. Acids are detected by type III taste receptor cells (TRCs), located in taste buds across the tongue and palate epithelium. The first step in sour taste transduction is believed to be entry of protons into the cell cytosol, which leads to cytosolic acidification and the generation of action potentials. The proton-selective ion channel Otop1 is expressed in type III TRCs and is a candidate sour receptor. Here, we tested the contribution of Otop1 to taste cell and gustatory nerve responses to acids in mice in which Otop1 was genetically inactivated (Otop1-KO mice). We first show that Otop1 is required for the inward proton current in type III TRCs from different parts of the tongue that are otherwise molecularly heterogeneous. We next show that in type III TRCs from Otop1-KO mice, intracellular pH does not track with extracellular pH and that moderately acidic stimuli do not elicit trains of action potentials, as they do in type III TRCs from wild-type mice. Moreover, gustatory nerve responses in Otop1-KO mice were severely and selectively attenuated for acidic stimuli, including citric acid and HCl. These results establish that the Otop1 proton channel plays a critical role in acid detection in the mouse gustatory system, evidence that it is a bona fide sour taste receptor.