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

Symptom management in amyotrophic lateral sclerosis: We can do better

Peer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/141321/1/mus25740_am.pdfhttps://deepblue.lib.umich.edu/bitstream/2027.42/141321/2/mus25740.pd

Hair cells of the mammalian cochlea: extraordinary nanomachines

In mammals, the sense of hearing relies on the normal function of two types of specialized cells: inner hair cells (IHC) and outer hair cells (OHC). They both possess the capacity to detect and convert mechanical movements within the cochlea, associated with sounds, into electrical potentials. A set of stereocilias in their apical end is where the mechano-electrical transduction actually occurs. IHC and OHC have very different functions within the complex process of hearing. IHC are responsible for transmitting the electrical information to the brain, for which they possess a specialized glutamatergic synapse with very unique properties. Neurotransmitter is released without pause and with high temporal precision, taking advantage of a synaptic organelle called the ribbon. OHC are exquisite piezoelectric devices, as changes in their membrane potential produce measurable changes in length. This capacity of OHC provides refined frequency selectivity and extra sensitivity to low intensity sounds. Interestingly, OHC function is regulated by an inhibitory innervation that descends from the brainstem and is mediated by acetylcholine. A very special type of nicotinic receptor, α9α10, participates in this synapse. Recent advances have shed light on the importance of this efferent control on acoustic trauma and higher hearing capabilities.Sociedad Argentina de Fisiologí

Divide and conquer acoustic diversity

Humans can recognize differences in sound intensity of up to 6 orders of magnitude. However, it is not clear how this is achieved and what enables our auditory systems to encode such a gradient. Özçete & Moser (2021) report in this issue that the key to this lies in the synaptic heterogeneity within individual sensory cells in the inner ear.Fil: Gomez Casati, Maria Eugenia. 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. Instituto de Farmacología; ArgentinaFil: Goutman, Juan Diego. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Investigaciones en Ingeniería Genética y Biología Molecular "Dr. Héctor N. Torres"; Argentin

En la aventura de los sonidos

Análisis de los constituyentes de la lengua, específicamente la relación existente entre el sonido y el significado. Los signos como sistema de la lengua y unidades de diferentes niveles que sirven para constituir lo que se desea

Use of Angle‐Independent M‐Mode Sonography for Assessment of Diaphragm Displacement

Peer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/137196/1/jum14204.pd

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

Postsynaptic Recordings at Afferent Dendrites Contacting Cochlear Inner Hair Cells: Monitoring Multivesicular Release at a Ribbon Synapse

The afferent synapse between the inner hair cell (IHC) and the auditory nerve fiber provides an electrophysiologically accessible site for recording the postsynaptic activity of a single ribbon synapse 1-4. Ribbon synapses of sensory cells release neurotransmitter continuously, the rate of which is modulated in response to graded changes in IHC membrane potential 5. Ribbon synapses have been shown to operate by multivesicular release, where multiple vesicles can be released simultaneously to evoke excitatory postsynaptic currents (EPSCs) of varying amplitudes 1, 4, 6-11. Neither the role of the presynaptic ribbon, nor the mechanism underlying multivesicular release is currently well understood