Transmitter release from cochlear hair cells is phase locked to cyclic stimuli of different intensities and frequencies

The auditory system processes time and intensity through separate brainstem pathways to derive spatial location as well as other salient features of sound. The independent coding of time and intensity begins in the cochlea, where afferent neurons can fire action potentials at constant phase throughout a wide range of stimulus intensities. We have investigated time and intensity coding by simultaneous presynaptic and postsynaptic recording at the hair cell-afferent synapse from rats. Trains of depolarizing steps to the hair cell were used to elicit postsynaptic currents that occurred at constant phase for a range of membrane potentials over which release probability varied significantly. To probe the underlying mechanisms, release was examined using single steps to various command voltages. As expected for vesicular release, first synaptic events occurred earlier as presynaptic calcium influx grew larger. However, synaptic depression produced smaller responses with longer first latencies. Thus, during repetitive hair cell stimulation, as the hair cell is more strongly depolarized, increased calcium channel gating hurries transmitter release, but the resulting vesicular depletion produces a compensatory slowing. Quantitative simulation of ribbon function shows that these two factors varied reciprocally with hair cell depolarization (stimulus intensity) to produce constant synaptic phase. Finally, we propose that the observed rapid vesicle replenishment would help maintain the vesicle pool, which in turn would equilibrate with the stimulus intensity (and therefore the number of open Ca 2+ channels), so that for trains of different levels the average phase will be conserved.Fil: Goutman, Juan Diego. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Investigaciones en Ingeniería Genética y Biología Molecular "Dr. Héctor N. Torres"; Argentin

Mechanisms of synaptic depression at the hair cell ribbon synapse that support auditory nerve function

Inner hair cells (IHCs) in the cochlea are the mammalian phono-receptors, transducing sound energy into graded changes in membrane potentials, the so called “receptor potentials.” Ribbon synapses between IHCs and auditory nerve neurons are responsible for converting receptor potentials into spike rates. The characteristics of auditory nerve responses to sound have been described extensively. For instance, persistent acoustic stimulation produces sensory adaptation, which is revealed as a reduction in neuronal spike rate with time constants in the range of milliseconds to seconds. Since the amplitude of IHC receptor potentials is invariant during this period, the classic hypothesis pointed to vesicle depletion at the IHC as responsible for auditory adaptation. In this study, we observed that fast synaptic depression occurred in responses to stimuli of varying intensities. Nevertheless, release continued after this initial depression, via synaptic vesicles with slower exocytotic kinetics. Heterogeneity in kinetic elements, therefore, favored synaptic responses with an early peak and a sustained phase. The application of cyclothiazide (CTZ) revealed that desensitization of postsynaptic receptors contributed to synaptic depression, which was more pronounced during stronger stimulation. Thus, desensitization had a twofold effect: It abbreviated signaling between IHC and the auditory nerve and also balanced differences in decay kinetics between responses to different stimulation strengths. We therefore propose that both pre- and postsynaptic mechanisms at the IHC ribbon synapse contribute to synaptic depression at the IHC ribbon synapse and spike rate adaptation in the auditory nerve.Fil: Goutman, Juan Diego. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Investigaciones en Ingeniería Genética y Biología Molecular "Dr. Héctor N. Torres"; Argentin

Coalition-proof supply function equilibria in oligopoly

In an industry where firms compete via supply functions, the set of equilibrium outcomes is large. If decreasing supply functions are ruled out, this set is reduced significantly, but remains large. Specifically, the set of prices that can be sustained by supply function equilibria is the interval between the competitive price and the Cournot price. In sharp contrast, when the number of firms is above a threshold we identify (e.g., three if demand is linear), only the Cournot outcome can be sustained by a coalition-proof supply function equilibrium.Publicad

Statistical description of eigenfunctions in chaotic and weakly disordered systems beyond universality

We present a semiclassical approach to eigenfunction statistics in chaotic and weakly disordered quantum systems which goes beyond Random Matrix Theory, supersymmetry techniques, and existing semiclassical methods. The approach is based on a generalization of Berry's Random Wave Model, combined with a consistent semiclassical representation of spatial two-point correlations. We derive closed expressions for arbitrary wavefunction averages in terms of universal coefficients and sums over classical paths, which contain, besides the supersymmetry results, novel oscillatory contributions. Their physical relevance is demonstrated in the context of Coulomb blockade physics

Natural models of theories of green points

We explicitly present expansions of the complex field which are models of the theories of green points in the multiplicative group case and in the case of an elliptic curve without complex multiplication defined over $\mathbb{R}$. In fact, in both cases we give families of structures depending on parameters and prove that they are all models of the theories, provided certain instances of Schanuel's conjecture or an analogous conjecture for the exponential map of the elliptic curve hold. In the multiplicative group case, however, the results are unconditional for generic choices of the parameters

"Wars are not something accidental, nor are they due to bad characters"

Interview with Dario Azzellini, author of The Business of War and the new documentary film, Comuna Under Construction. What is it about Venezuela that is so interesting? Since 2003 I have practically lived in Venezuela. What motivates me is that I am interested in the social transformation process happening here. It’s a different type of revolution, a new left that draws from all the experiences of the 60s, 70s, 80s and 90s. ..