A5047620895- Hearing, Cochlea, Tinnitus, Genetics
- Nicotinic Acetylcholine Receptors Study
- Hearing Loss and Rehabilitation
- Ion channel regulation and function
- Vestibular and auditory disorders
- Ion Channels and Receptors
- Biochemical Analysis and Sensing Techniques
- Photoreceptor and optogenetics research
- Neuroscience and Neuropharmacology Research
- Receptor Mechanisms and Signaling
- Stress Responses and Cortisol
- Mosquito-borne diseases and control
- Antimicrobial Peptides and Activities
- Mass Spectrometry Techniques and Applications
- Microbial Metabolic Engineering and Bioproduction
- Noise Effects and Management
- Immune Response and Inflammation
- Advanced Proteomics Techniques and Applications
- Advanced Chemical Sensor Technologies
- Insect and Pesticide Research
- Wnt/β-catenin signaling in development and cancer
- Circadian rhythm and melatonin
- vaccines and immunoinformatics approaches
- Gene expression and cancer classification
- Kruppel-like factors research
University of Mississippi Medical Center
2013-2023
Estée Lauder (United States)
2019
State Street (United States)
2016
Tufts University
2002-2011
Salk Institute for Biological Studies
1993-2002
University of Buenos Aires
2001
University of Connecticut
1985-1993
We report the cloning and characterization of rat α10, a previously unidentified member nicotinic acetylcholine receptor (nAChR) subunit gene family. The protein encoded by α10 nAChR is most similar to α9 nAChR, both genes are transcribed in adult mechanosensory hair cells. Injection Xenopus laevis oocytes with cRNA alone or pairwise combinations either α2-α6 β2-β4 cRNAs yielded no detectable ACh-gated currents. However, coinjection resulted appearance an unusual subtype. Compared homomeric...
Abstract We have produced a neurochemical map of the cell bodies origin cochlear efferent terminals in rat by combining glutamic acid decarboxylase (GAD), choline acetyltransferase (ChAT) or calcitonin gene‐related peptide (CGRP)immunocytochemistry with retrograde transport horseradish peroxidase. The location are general agreement medial and lateral systems described White Warr ( J. Comp. Neurol. 219:203–214, 1983) some minor modifications. system consists at least two pools chemically...
Significance This study addresses the need to phase out opioids as major analgesic drugs for moderate severe chronic pain. We establish that a highly selective and potent inhibitor of α9α10 nicotinic acetylcholine receptor (nAChR) subtype prevents expression chemotherapy-induced neuropathic Thus, antagonists nAChR are potential leads nonopioid drug development. The effects inhibitors receptor, together with genetic studies, suggest key role in an intercellular signaling network can be...
In the mature cochlea, inner hair cells (IHCs) transduce acoustic signals into receptor potentials, communicating to brain by synaptic contacts with afferent fibers. Before onset of hearing, a transient efferent innervation is found on IHCs, mediated nicotinic cholinergic that may contain both α9 and α10 subunits. Calcium influx through activates calcium-dependent (SK2-containing) potassium channels. This inhibitory synapse thought disappear after hearing [after postnatal day 12 (P12)]. We...
In the rat central nervous system, mRNA encoding N-methyl-D-aspartate receptor subunit R1 is most ubiquitously distributed among cloned mRNAs of this glutamate subtype. The very abundantly expressed and coexpression necessary for functional expression all other subunits. Therefore, likely to be an essential component known receptors in brain. By employing sequence specific polyclonal antibodies, we demonstrate that brain R1, as well recombinantly protein, has apparent molecular mass 116 kDa...
Several ganglionic nicotinic acetylcholine receptor (nAChR) types are abundantly expressed in nonneuronal locations, but their functions remain unknown. We found that keratinocyte α7 nAChR controls homeostasis and terminal differentiation of epidermal keratinocytes required for formation the skin barrier. The effects functional inactivation on cell cycle progression, differentiation, apoptosis were studied monolayers treated with α-bungarotoxin or antisense oligonucleotides Acra7 homozygous...
Programmed cell death regulates a number of biological phenomena, and the apoptotic signal must itself be tightly controlled to avoid inappropriate death. We established genetic screen search for molecules that inhibit from Fas receptor. Here we report isolation gene, LFG, protects cells uniquely but not mechanistically related tumor necrosis factor α signal. LFG is widely distributed, remarkably highly expressed in hippocampus. can bind receptor, does regulate expression or interfere with...
The retinoblastoma protein pRb is required for cell-cycle exit of embryonic mammalian hair cells but not their early differentiation. However, its role in postnatal unknown. To study the function mature animals, we created a new conditional mouse model, with Rb gene deleted primarily inner ear. Progeny survive up to 6 months. During development, −/− continue divide and can transduce mechanical stimuli. adult mice exhibit profound hearing loss due progressive degeneration organ Corti. We show...
The transduction of sound in the auditory periphery, cochlea, is inhibited by efferent cholinergic neurons projecting from brainstem and synapsing directly on mechanosensory hair cells. One fundamental question neuroscience what role(s) this feedback plays our ability to hear. In present study, we have engineered a genetically modified mouse model which magnitude duration effects are increased, assess consequences manipulation cochlear function. We generated Chrna9L9'T line knockin mice with...
Although homomeric channels assembled from the alpha9 nicotinic acetylcholine receptor (nAChR) subunit are functional in vitro, electrophysiological, anatomical, and molecular data suggest that native cholinergic olivocochlear function is mediated via heteromeric nAChRs composed of both alpha10 subunits. To gain insight into vivo, we examined olivo cochlear innervation null-mutant mice. Electrophysiological recordings postnatal (P) days P8-9 inner hair cells revealed ACh-gated currents...
Spontaneous electrical activity generated by developing sensory cells and neurons is crucial for the maturation of neural circuits. The full mammalian auditory inner hair (IHCs) depends on patterns spontaneous action potentials during a ‘critical period’ development. intrinsic spiking IHCs can be modulated inhibitory input from cholinergic efferent fibres descending brainstem, which transiently innervate immature IHCs. However, it remains unknown whether this transient to required their...
Outer hair cells in the mammalian cochlea receive a cholinergic efferent innervation that constitutes effector arm of sound-evoked negative feedback loop. The well-studied suppressive effects acetylcholine (ACh) release from terminals are mediated by alpha9/alpha10 ACh receptors and potently blocked strychnine. Here, we report novel, efferent-mediated enhancement cochlear neural responses otoacoustic emissions mice. In controls, slow response amplitude to supranormal levels appears after...
Cells of the inner ear face constant metabolic and structural stress. Exposure to intense sound or certain drugs destroys cochlea hair cells, which in mammals do not regenerate. Thus, an endogenous stress response system may exist within protect it from everyday stressors. We recently described existence corticotropin-releasing factor (CRF) mouse cochlea. The CRF receptor type 1 (CRFR1) is considered primary canonical target signaling, systemically plays essential role coordinating body-wide...