A5022399946- Hearing, Cochlea, Tinnitus, Genetics
- Nicotinic Acetylcholine Receptors Study
- Hearing Loss and Rehabilitation
- Receptor Mechanisms and Signaling
- Ion channel regulation and function
- Marine animal studies overview
- Biochemical Analysis and Sensing Techniques
- Photoreceptor and optogenetics research
- Vestibular and auditory disorders
- Animal Vocal Communication and Behavior
- Neuroscience and Neuropharmacology Research
- Noise Effects and Management
- Neurogenesis and neuroplasticity mechanisms
- Ion Channels and Receptors
- Cholinesterase and Neurodegenerative Diseases
- Bat Biology and Ecology Studies
- Memory and Neural Mechanisms
- Biochemical and Molecular Research
- Neonatal Respiratory Health Research
- Neuroendocrine regulation and behavior
- Enzyme Structure and Function
- Amino Acid Enzymes and Metabolism
- Neuroscience of respiration and sleep
- Enzyme Catalysis and Immobilization
- Acoustic Wave Phenomena Research
University of Buenos Aires
2006-2025
Consejo Nacional de Investigaciones Científicas y Técnicas
2004-2025
Experimental Medicine and Biology Institute
2004-2019
Institute of Astronomy and Space Physics
2005-2015
Boston Children's Hospital
2010-2014
Harvard University
2009-2014
Boston Children's Museum
2009
Children's Hospital
2009
Centro de Estudios Fotosintéticos y Bioquímicos
2002-2003
National University of Rosario
2003
Neurotrophin-3 (Ntf3) and brain derived neurotrophic factor (Bdnf) are critical for sensory neuron survival establishment of neuronal projections to epithelia in the embryonic inner ear, but their postnatal functions remain poorly understood. Using cell-specific inducible gene recombination mice we found that, Bbnf Ntf3 required formation maintenance hair cell ribbon synapses vestibular cochlear epithelia, respectively. We also show that supporting cells these key endogenous source...
The α9 and α10 nicotinic acetylcholine receptor (nAChR) subunits assemble to form the α9α10 nAChR subtype. This is believed mediate cholinergic synaptic transmission between efferent olivocochlear fibers hair cells of cochlea. In addition and/or expression has been described in dorsal root ganglion neurons, lymphocytes, skin keratinocytes, pars tuberalis pituitary. Specific antagonists that selectively block channel could be valuable tools for elucidating its role these diverse tissues....
Cochlear synaptopathy produced by exposure to noise levels that cause only transient auditory threshold elevations is a condition affects many people and believed contribute poor speech discrimination in noisy environments. These functional deficits hearing, without changes sensitivity, have been called hidden hearing loss (HHL). It has proposed activity of the medial olivocochlear (MOC) system can ameliorate acoustic trauma effects. Here we explore role MOC HHL comparing performance two...
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...
Recent studies indicate that molecules released by glia can induce synapse formation. However, what induces to produce such signals, their identity, and in vivo relevance remain poorly understood. Here we demonstrate supporting cells of the vestibular organ—cells have many characteristics glia—promote formation only when induced neuron-derived signals. Furthermore, identify BDNF as synaptogenic signal produced these nonneuronal cells. Mice which erbB signaling has been eliminated dysfunction...
The α9 and α10 nicotinic cholinergic subunits assemble to form the receptor that mediates synaptic transmission between efferent olivocochlear fibers hair cells of cochlea. They are latest vertebrate (nAChR) have been cloned, their identification has established a distant early divergent branch within nAChR gene family. subunit serves as “structural” component leading heteromeric α9α10 nAChRs with distinct properties. We now probed stoichiometry recombinant expressed in Xenopus oocytes. made...
Before the onset of hearing, a transient efferent innervation is found on inner hair cells (IHCs). This synapse inhibitory and mediated by nicotinic cholinergic receptor (nAChR) probably formed α9 α10 subunits. We analysed pharmacological biophysical characteristics native nAChR using whole‐cell recordings from IHCs in acutely excised apical turns rat organ Corti. Nicotine did not activate but rather blocked acetylcholine (ACh)‐evoked currents with an IC 50 1 ± 0.1 μ m . Antagonists...
Significance Age-related hearing loss is the most common cause of loss. Here, we show that medial olivocochlear feedback mediates resistance to age-related loss—presbycusis—and this occurs via α9α10 cholinergic nicotinic receptor complexes on outer hair cells. These findings are particularly promising because they provide a proof principle supporting enhancement system as viable approach for prevention or treatment Therefore, it opens way design novel positive modulators nAChR receptors...
ABSTRACT Periodic spontaneous activity is a key feature of developing sensory systems, essential for the formation and refinement neural circuits. Before onset hearing in altricial mammals, cochlear inner hair cells exhibit electrical that activates primary afferents to propagate into central nervous system. This activity, modulated by medial olivocochlear efferent feedback via α9α10 nicotinic cholinergic receptors present cells, crucial auditory system maturation. In this study, we examined...
In this study, we report the effects of quinoline derivatives quinine, its optical isomer quinidine, and chloroquine on α9α10-containing nicotinic acetylcholine receptors (nAChRs). The compounds blocked (ACh)-evoked responses in α9α10-injected <i>Xenopus laevis</i> oocytes a concentration-dependent manner, with rank order potency (IC<sub>50</sub> = 0.39 μM) > quinine 0.97 ∼ quinidine 1.37 μM). Moreover, ACh-evoked rat cochlear inner hair cells an IC<sub>50</sub> value 0.13 μM, which is...
The synapse between olivocochlear (OC) neurons and cochlear mechanosensory hair cells is cholinergic, fast, inhibitory. inhibitory sign of this cholinergic accounted for by the activation Ca 2+ -permeable postsynaptic α9α10 nicotinic receptors coupled to opening hyperpolarizing -activated small-conductance type 2 (SK2)K + channels. Acetylcholine (ACh) release at supported both P/Q- N-type voltage-gated calcium channels (VGCCs). Although OC an abundant GABA innervation present along mammalian...
The auditory system in many mammals is immature at birth but precisely organized adults. Spontaneous activity the inner ear plays a critical role guiding this maturation process. This shaped by an efferent pathway that descends from brainstem and makes transient direct synaptic contacts with hair cells. In work, we used α9 cholinergic nicotinic receptor knock-in mouse model (of either sex) enhanced medial (<i>Chrna9L9</i>′<i>T</i>, <i>L9</i>′<i>T</i>) to further understand of olivocochlear...
Abstract Sound is an important part of man's contact with the environment and has served as critical means for survival throughout his evolution. As a result exposure to noise, physiological functions such those involving structures auditory non‐auditory systems might be damaged. We have previously reported that noise‐exposed developing rats elicited hippocampal‐related histological, biochemical behavioral changes. However, no data about time lapse these changes were reported. Moreover,...
We have performed a systematic mutagenesis of three hydrophobic rings (17', 13' and 9') within transmembrane region (TM) 2 the alpha9alpha10 nicotinic cholinergic receptor (nAChR) to hydrophilic (threonine) residue compared properties mutant receptors reconstituted in Xenopus laevis oocytes. Phenotypic changes were evidenced by decrease desensitization rate, an increase both EC(50) for ACh as well efficacy partial agonists reduction allosteric modulation extracellular Ca(2+). Mutated...
During development, inner hair cells (IHCs) in the mammalian cochlea are unresponsive to acoustic stimuli but instead exhibit spontaneous activity. this same period, neurons originating from medial olivocochlear complex (MOC) transiently innervate IHCs, regulating their firing pattern which is crucial for correct development of auditory pathway. Although MOC-IHC a cholinergic synapse, previous evidence indicates widespread presence gamma-aminobutyric acid (GABA) signaling markers, including...
Exposure of developing rats to noise has shown induce hippocampal-related behavioral alterations that were prevented after a week housing in an enriched environment. However, neither the effect repeated exposures nor its impact on key endogenous antioxidants had been studied yet. Thus, aim present work was reveal novel data about hippocampal oxidative state through measurement possible age-related differences levels thioredoxins exposed at different developmental ages and subjected schemes...
Noise-induced hearing loss has gained relevance as one of the most common forms impairment. The anatomical correlates loss, principally cell damage and/or death, are relatively well-understood histologically. However, much less is known about physiological aspects damaged, surviving cells. Here we addressed functional consequences noise exposure on capacity inner hair cells (IHCs) to release synaptic vesicles at synapses with spiral ganglion neurons (SGNs). Mice either sex postnatal day (P)...