A "synaptoplasmic cistern" mediates rapid inhibition of cochlear hair cells

Cochlear hair cells are inhibited by cholinergic efferent neurons. The acetylcholine (ACh) receptor of the hair cell is a ligand-gated cation channel through which calcium enters to activate potassium channels and hyperpolarize the cell. It has been proposed that calcium-induced calcium release (CICR) from a near-membrane postsynaptic store supplements this process. Here, we demonstrate expression of type I ryanodine receptors in outer hair cells in the apical turn of the rat cochlea. Consistent with this finding, ryanodine and other store-active compounds alter the amplitude of transient currents produced by synaptic release of ACh, as well as the response of the hair cell to exogenous ACh. Like the sarcoplasmic reticulum of muscle, the "synaptoplasmic" cistern of the hair cell efficiently couples synaptic input to CICR.Fil: Lioudyno, Maria. Johns Hopkins University School of Medicine; Estados UnidosFil: Hiel, Hakim. Johns Hopkins University School of Medicine; Estados UnidosFil: Kong, Jee-Hyun. Johns Hopkins University School of Medicine; Estados UnidosFil: Katz, Eleonora. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Investigaciones en Ingeniería Genética y Biología Molecular "Dr. Héctor N. Torres"; ArgentinaFil: Waldman, Erik. Johns Hopkins University School of Medicine; Estados UnidosFil: Parameshwaran Iyer, Suchitra. Johns Hopkins University School of Medicine; Estados UnidosFil: Glowatzki, Elisabeth. Johns Hopkins University School of Medicine; Estados UnidosFil: Fuchs, Paul A.. Johns Hopkins University School of Medicine; Estados Unido

Short-term synaptic plasticity regulates the level of olivocochlear inhibition to auditory hair cells

In the mammalian inner ear, the gain control of auditory inputs is exerted by medial olivocochlear (MOC) neurons that innervate cochlear outer hair cells (OHCs). OHCs mechanically amplify the incoming sound waves by virtue of their electromotile properties while the MOC system reduces the gain of auditory inputs by inhibiting OHC function. How this process is orchestrated at the synaptic level remains unknown. In the present study, MOC firing was evoked by electrical stimulation in an isolated mouse cochlear preparation, while OHCs postsynaptic responses were monitored by whole-cell recordings. These recordings confirmed that electrically evoked IPSCs (eIPSCs) are mediated solely by α9β10 nAChRs functionally coupled to calcium-activated SK2 channels. Synaptic release occurred with low probability when MOC-OHC synapses were stimulated at 1 Hz. However, as the stimulation frequency was raised, the reliability of release increased due to presynaptic facilitation. In addition, the relatively slow decay of eIPSCs gave rise to temporal summation at stimulation frequencies >10 Hz. The combined effect of facilitation and summation resulted in a frequency-dependent increase in the average amplitude of inhibitory currents in OHCs. Thus, we have demonstrated that short-term plasticity is responsible for shaping MOC inhibition and, therefore, encodes the transfer function from efferent firing frequency to the gain of the cochlear amplifier.Fil: Ballestero, Jimena Andrea. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Investigaciones en Ingeniería Genética y Biología Molecular "Dr. Héctor N. Torres"; ArgentinaFil: Zorrilla de San Martín, Javier. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Investigaciones en Ingeniería Genética y Biología Molecular "Dr. Héctor N. Torres"; ArgentinaFil: Goutman, Juan Diego. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Investigaciones en Ingeniería Genética y Biología Molecular "Dr. Héctor N. Torres"; ArgentinaFil: Elgoyhen, Ana Belen. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Investigaciones en Ingeniería Genética y Biología Molecular "Dr. Héctor N. Torres"; Argentina. Universidad de Buenos Aires. Facultad de Medicina; ArgentinaFil: Fuchs, Paul A.. The Johns Hopkins University School of Medicine; Estados UnidosFil: Katz, Eleonora. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Investigaciones en Ingeniería Genética y Biología Molecular "Dr. Héctor N. Torres"; Argentina. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Departamento de Fisiología, Biología Molecular y Celular; Argentin

A point mutation in the hair cell nicotinic cholinergic receptor prolongs cochlear inhibition and enhances noise protection

The transduction of sound in the auditory periphery, the cochlea, is inhibited by efferent cholinergic neurons projecting from the brainstem and synapsing directly on mechanosensory hair cells. One fundamental question in auditory neuroscience is what role(s) this feedback plays in our ability to hear. In the present study, we have engineered a genetically modified mouse model in which the magnitude and duration of efferent cholinergic effects are increased, and we assess the consequences of this manipulation on cochlear function. We generated the Chrna9L9′T of knockin mice with a threonine for leucine change (L9′T) at position 9′ of the second transmembrane domain of the α9 nicotinic cholinergic subunit, rendering α9-containing receptors that were hypersensitive to acetylcholine and had slower desensitization kinetics. The Chrna9L9′T allele produced a 3-fold prolongation of efferent synaptic currents in vitro. In vivo, Chrna9L9′T mice had baseline elevation of cochlear thresholds and efferent-mediated inhibition of cochlear responses was dramatically enhanced and lengthened: both effects were reversed by strychnine blockade of the α9α10 hair cell nicotinic receptor. Importantly, relative to their wild-type littermates, Chrna9L9′T/L9′T mice showed less permanent hearing loss following exposure to intense noise. Thus, a point mutation designed to alter α9α10 receptor gating has provided an animal model in which not only is efferent inhibition more powerful, but also one in which sound-induced hearing loss can be restrained, indicating the ability of efferent feedback to ameliorate sound trauma.Fil: Taranda, Julian. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Investigaciones en Ingeniería Genética y Biología Molecular "Dr. Héctor N. Torres"; Argentina. Tufts University School of Medicine; Estados UnidosFil: Maison, Stéphane F.. Massachusetts Eye and Ear Infirmary; Estados UnidosFil: Ballestero, Jimena Andrea. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Investigaciones en Ingeniería Genética y Biología Molecular "Dr. Héctor N. Torres"; ArgentinaFil: Katz, Eleonora. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Investigaciones en Ingeniería Genética y Biología Molecular "Dr. Héctor N. Torres"; ArgentinaFil: Savino, Jessica. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Investigaciones en Ingeniería Genética y Biología Molecular "Dr. Héctor N. Torres"; ArgentinaFil: Vetter, Douglas E.. Tufts University School of Medicine; Estados UnidosFil: Boulter, Jim. University of California at Los Angeles; Estados UnidosFil: Liberman, M. Charles. Massachusetts Eye and Ear Infirmary; Estados UnidosFil: Fuchs, Paul A.. The Johns Hopkins University School of Medicine; Estados UnidosFil: Elgoyhen, Ana Belen. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Investigaciones en Ingeniería Genética y Biología Molecular "Dr. Héctor N. Torres"; Argentina. Universidad de Buenos Aires. Facultad de Medicina. Departamento de Farmacología; Argentin

Treatment of peroneal nerve injuries with simultaneous tendon transfer and nerve exploration

Abstract Background Common peroneal nerve palsy leading to foot drop is difficult to manage and has historically been treated with extended bracing with expectant waiting for return of nerve function. Peroneal nerve exploration has traditionally been avoided except in cases of known traumatic or iatrogenic injury, with tendon transfers being performed in a delayed fashion after exhausting conservative treatment. We present a new strategy for management of foot drop with nerve exploration and concomitant tendon transfer. Method We retrospectively reviewed a series of 12 patients with peroneal nerve palsies that were treated with tendon transfer from 2005 to 2011. Of these patients, seven were treated with simultaneous peroneal nerve exploration and repair at the time of tendon transfer. Results Patients with both nerve repair and tendon transfer had superior functional results with active dorsiflexion in all patients, compared to dorsiflexion in 40% of patients treated with tendon transfers alone. Additionally, 57% of patients treated with nerve repair and tendon transfer were able to achieve enough function to return to running, compared to 20% in patients with tendon transfer alone. No patient had full return of native motor function resulting in excessive dorsiflexion strength. Conclusion The results of our limited case series for this rare condition indicate that simultaneous nerve repair and tendon transfer showed no detrimental results and may provide improved function over tendon transfer alone.http://deepblue.lib.umich.edu/bitstream/2027.42/109530/1/13018_2014_Article_67.pd

The Search for Supernova-produced Radionuclides in Terrestrial Deep-sea Archives

An enhanced concentration of 60Fe was found in a deep ocean's crust in 2004 in a layer corresponding to an age of ~2 Myr. The confirmation of this signal in terrestrial archives as supernova-induced and detection of other supernova-produced radionuclides is of great interest. We have identified two suitable marine sediment cores from the South Australian Basin and estimated the intensity of a possible signal of the supernova-produced radionuclides 26Al, 53Mn, 60Fe and the pure r-process element 244Pu in these cores. A finding of these radionuclides in a sediment core might allow to improve the time resolution of the signal and thus to link the signal to a supernova event in the solar vicinity ~2 Myr ago. Furthermore, it gives an insight on nucleosynthesis scenarios in massive stars, the condensation into dust grains and transport mechanisms from the supernova shell into the solar system

Boundary Conditions in Rational Conformal Field Theories

We develop further the theory of Rational Conformal Field Theories (RCFTs) on a cylinder with specified boundary conditions emphasizing the role of a triplet of algebras: the Verlinde, graph fusion and Pasquier algebras. We show that solving Cardy's equation, expressing consistency of a RCFT on a cylinder, is equivalent to finding integer valued matrix representations of the Verlinde algebra. These matrices allow us to naturally associate a graph $G$ to each RCFT such that the conformal boundary conditions are labelled by the nodes of $G$. This approach is carried to completion for $sl(2)$ theories leading to complete sets of conformal boundary conditions, their associated cylinder partition functions and the $A$-$D$-$E$ classification. We also review the current status for WZW $sl(3)$ theories. Finally, a systematic generalization of the formalism of Cardy-Lewellen is developed to allow for multiplicities arising from more general representations of the Verlinde algebra. We obtain information on the bulk-boundary coefficients and reproduce the relevant algebraic structures from the sewing constraints.Comment: 71 pages. Minor changes with respect to 2nd version. Recently published in Nucl.Phys.B but mistakenly as 1st version. Will be republished in Nucl.Phys.B as this (3rd) versio

Continuous-variable optical quantum state tomography

This review covers latest developments in continuous-variable quantum-state tomography of optical fields and photons, placing a special accent on its practical aspects and applications in quantum information technology. Optical homodyne tomography is reviewed as a method of reconstructing the state of light in a given optical mode. A range of relevant practical topics are discussed, such as state-reconstruction algorithms (with emphasis on the maximum-likelihood technique), the technology of time-domain homodyne detection, mode matching issues, and engineering of complex quantum states of light. The paper also surveys quantum-state tomography for the transverse spatial state (spatial mode) of the field in the special case of fields containing precisely one photon.Comment: Finally, a revision! Comments to lvov(at)ucalgary.ca and raymer(at)uoregon.edu are welcom