A5037947412- Hearing, Cochlea, Tinnitus, Genetics
- Ear Surgery and Otitis Media
- Hearing Loss and Rehabilitation
- Vestibular and auditory disorders
- Immune Response and Inflammation
- Antimicrobial Peptides and Activities
- Ear and Head Tumors
- Otitis Media and Relapsing Polychondritis
- Neuroscience of respiration and sleep
- Pediatric health and respiratory diseases
- Respiratory and Cough-Related Research
- Noise Effects and Management
- Neural dynamics and brain function
- Adenosine and Purinergic Signaling
- Cell Adhesion Molecules Research
- Congenital Ear and Nasal Anomalies
- Proteoglycans and glycosaminoglycans research
- Biochemical Analysis and Sensing Techniques
- NF-κB Signaling Pathways
- Acoustic Wave Phenomena Research
- Sinusitis and nasal conditions
- Bacterial Infections and Vaccines
- Nerve injury and regeneration
- Muscle Physiology and Disorders
- Ion Channels and Receptors
University of California, San Diego
2016-2025
VA San Diego Healthcare System
2015-2025
San Diego State University
2025
Otonomy (United States)
2024
United States Department of Veterans Affairs
1994-2022
Veterans Health Administration
2021
University of San Diego
2021
University of California San Diego Medical Center
1989-2020
UC San Diego Health System
2012-2020
Universidad Católica Santo Domingo
2014
The molecular mechanisms dictating the morphogenesis and differentiation of mammalian inner ear are largely unknown. To better elucidate normal development this organ, two approaches were taken. First, membranous labyrinths mouse ears ranging from 10.25 to 17 d postcoitum (dpc) filled with paint reveal their gross development. Particular attention was focused on developing utricle, saccule, cochlea. Second, we used bone morphogenetic protein 4 (BMP4) lunatic fringe (Fng) as markers identify...
Mongolian gerbils were trained to respond pure tones in a shock-avoidance task. The animals proved be readily trainable and behaviorally stable. Thresholds obtained by method of limits and, the case one animal, generating psychrometric functions. gerbil responds frequencies between 0.1 60.0 kHz. For 1.0 16.0 kHz, threshold hearing averages 4.6 dB SPL. Between sensitivity declines at rate 12 dB/octave. 40.0 increases 13 dB/octave, above kHz 66 derived from psychometric functions essentially...
Exposure to intense sound or noise can result in purely temporary threshold shift (TTS), leave a residual permanent (PTS) along with alterations growth functions of auditory nerve output. Recent research has revealed number mechanisms that contribute noise-induced hearing loss (NIHL). The principle cause NIHL is damage cochlear hair cells and associated synaptopathy. Contributions TTS include reversible cell (HC) stereocilia synapses, while moderate reflects protective purinergic adaptation....
The distribution of the P2X2 receptor subunit adenosine 5'-triphosphate (ATP)-gated ion channels was examined in adult rat central nervous system (CNS) by using receptor-specific antisera and riboprobe-based situ hybridisation. mRNA expression matched protein localisation. An extensive pattern observed, including: olfactory bulb, cerebral cortex, hippocampus, habenula, thalamic subthalamic nuclei, caudate putamen, posteromedial amygdalo-hippocampal amygdalo-cortical substantia nigra pars...
Humans and chimpanzees share >99% identity in most proteins. One rare difference is a human-specific inactivating deletion the CMAH gene, which determines biosynthesis of sialic acid N-glycolylneuraminic (Neu5Gc). Since Neu5Gc prominent on chimpanzee cell surfaces, this mutation could have affected multiple systems. However, found human cancers fetuses trace amounts normal tissues, suggesting an alternate biosynthetic pathway. We inactivated mouse Cmah gene studied vivo consequences. There...
Deafness is the most common form of sensory impairment in human population and frequently caused by recessive mutations. To obtain animal models for forms deafness to identify genes that control development function auditory sense organs, we performed a forward genetics screen mice. We identified 13 mouse lines with defects six vestibular defects. mapped several affected genetic loci point mutations four genes. Interestingly, all are expressed mechanosensory hair cells required their...
Abstract The uptake of 2‐deoxyglucose (2‐DG) was employed to map functional activation the central auditory pathway in mongolian gerbil, during 85 dB SPL stimulation with pure tonal stimuli at frequencies 0.75, 3.0, or 12.0 kHz. Pure tones produced foci very high 2‐DG uptake, when compared adjacent tissue, cochlear nucleus, superior olivary complex, and inferior colliculus. Less distinct areas elevated were seen dorsal ventral nuclei lateral lemniscus, medial geniculate cortex. Little no...
Age-related hearing loss and noise-induced are major causes of human morbidity. Here we used genetics functional studies to show that a shared cause these disorders may be function the ATP-gated P2X(2) receptor (ligand-gated ion channel, purinergic 2) is expressed in sensory supporting cells cochlea. Genomic analysis dominantly inherited, progressive sensorineural DFNA41 six-generation kindred revealed rare heterozygous allele, P2RX2 c.178G > T (p.V60L), at chr12:133,196,029, which...
The response to repetitive stimulation of single cells in the auditory cortex monkey is dependent upon behavioral performance and training subject a simple discrimination task. In trained, performing animal, are more responsive than animal that trained but not naive monkey, evoked responses labile maintained only with nonrepetitive stimuli.
The sense of hearing is remarkable for its auditory dynamic range, which spans more than 10(12) in acoustic intensity. mechanisms that enable the cochlea to transduce high sound levels without damage are key interest, particularly with regard broad impact industrial, military, and recreational overstimulation on disability. We show ATP-gated ion channels assembled from P2X2 receptor subunits necessary development temporary threshold shift (TTS), evident brainstem response recordings as rise....
Abstract Tinnitus is a heritable, highly prevalent auditory disorder treated by multiple medical specialties. Previous GWAS indicated high genetic correlations between tinnitus and hearing loss, with little indication of differentiating signals. We present meta-analysis, triple previous sample sizes, expand to non-European ancestries. in 596,905 Million Veteran Program subjects identified 39 loci, genes related neuronal synapses cochlear structural support. Applying state-of-the-art analytic...
Extracellular ATP has multimodal actions in the cochlea affecting hearing sensitivity. ATP-gated ion channels involved this process were characterized guinea pig cochlea. Voltage-clamped hair cells exhibited a P2 receptor pharmacology compatible with assembly of from P2X 2 subunits. Reverse transcription-PCR experiments confirmed expression 2–1 subunit mRNA isoform sensory epithelium (organ Corti); splice variant that confers desensitization, 2–2 , was predominant expressed by primary...
Eccentric contractions (ECs), in which a muscle is forced to lengthen while activated, result injury and, eventually, strengthening and prevention of further injury. Although the mechanical basis EC-induced has been studied detail, biological response less well characterized. This study presents development minimally invasive model EC mouse, follows time course torque recovery after an injurious bout ECs, uses Affymetrix microarrays compare gene expression profile 48 h ECs both isometrically...
Abstract Background The mechanisms that consolidate neural circuitry are a major focus of neuroscience. In the mammalian cochlea, refinement spiral ganglion neuron (SGN) innervation to inner hair cells (by type I SGNs) and outer II is accompanied by 25% loss SGNs. Results We investigated segregation neuronal in mouse cochlea using β-tubulin peripherin antisera immunolabel all SGNs selectively SGNs, respectively, discovered it SGN population predominately lost within first postnatal week....
Abstract The dynamic adjustment of hearing sensitivity and frequency selectivity is mediated by the medial olivocochlear efferent reflex, which suppresses gain ‘cochlear amplifier’ in each ear. Such feedback important for promoting discrimination sounds background noise, sound localization protecting cochleae from acoustic overstimulation. However, sensory driver reflex unknown. Here, we resolve this longstanding question using a mouse model null gene encoding type III intermediate filament...