Efferent feedback onto sensory organs provides a means to modulate input the central nervous system. In developing mammalian cochlea, inner hair cells are transiently innervated by efferent fibers, even before function begins. Here, we show that neonatal inhibited cholinergic synaptic onset of hearing. The currents, as well cell's response acetylcholine, mediated nicotinic (alpha9-containing) receptor and result in activation small-conductance calcium-dependent potassium channels.

At the first synapse in auditory pathway, receptor potential of mechanosensory hair cells is converted into a firing pattern nerve fibers. For accurate coding timing and intensity sound signals, transmitter release at this must occur with highest precision. To measure directly transfer characteristics cell afferent synapse, we implemented simultaneous whole-cell recordings from mammalian inner (IHCs) fiber terminals that typically receive input single ribbon synapse. During 1-s IHC...

Cochlear inner hair cells (IHCs) convert sounds into receptor potentials and via their ribbon synapses firing rates in auditory nerve fibers. Multivesicular release at individual IHC activates AMPA-mediated EPSCs with widely ranging amplitudes. The underlying mechanisms specific role for multivesicular encoding sound are not well understood. Here we characterize the waveforms of recorded from afferent boutons contacting IHCs compare characteristics immature rats (postnatal days 8–11) hearing...

Significance Painfully loud sound causes protective or withdrawal responses, rather than continued listening. This differential behavior invites comparison with somatic pain responses driven by the anatomically distinct subset of small-diameter, unmyelinated afferents—C fibers. Like C fibers, type II cochlear afferents differ in size, number, and innervation pattern from I that encode sound. Here, we show are excited during tissue damage part algogenic cytoplasmic metabolite adenosine...

Type I spiral ganglion neurons (SGNs) are the auditory afferents that transmit sound information from cochlear inner hair cells (IHCs) to brainstem. These consist of physiological subtypes differ in their spontaneous firing rate (SR), activation threshold, and dynamic range have been described as low, medium, high SR fibers. Lately, single-cell RNA sequencing experiments revealed three molecularly defined type SGN subtypes. The extent which correspond is unclear. To address this question, we...

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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...

Large subtype‐specific differences in the sensitivity of cloned inward‐rectifier K + channels IRK1, BIR10 and ROMK1 subtype to being blocked by intracellular spermine (SPM) are described. It is shown, site‐directed mutagenesis, that four orders magnitude larger SPM compared may be explained a difference single amino acid putative transmembrane segment TMII. This residue, negatively charged glutamate BIR10, homologous residue IRK1 which has previously been shown change gating properties Mg 2+...

The P2X3 receptor is an ATP-gated ion channel predominantly expressed in nociceptive neurons from the dorsal root ganglion. channels are highly sensory and probably contribute to sensation of pain. Kinetics currents characterized by rapid desensitization (<100 ms) slow recovery (>20 s). Thus, any mechanism modulating rate and/or may have profound effect on susceptibility expressing ATP. Here we show that mediated heteromeric P2X2/3 composed P2X2 subunits potentiated neuropeptides substance P...

In mammals, auditory hair cells are generated only during embryonic development and loss or damage to is permanent. However, in non-mammalian vertebrate species, such as birds, neighboring glia-like supporting regenerate by both mitotic non-mitotic mechanisms. Based on work intact cochlear tissue, it thought that Notch signaling might restrict cell plasticity the mammalian cochlea. unresolved how functions cell-damaged cochlea molecular cellular changes induced response trauma poorly...

Synaptic transmission at the inner hair cell (IHC) afferent synapse, first synapse in auditory pathway, is specialized for rapid and reliable signaling. Here we investigated properties of a hyperpolarization-activated current (I(h)), expressed dendrite nerve fibers, its role shaping postsynaptic activity. We used whole patch-clamp recordings from dendrites directly where they contact IHC excised postnatal rat cochlear turns. Excitatory potentials (EPSPs) variable amplitude (1-35 mV) were...

In the vestibular periphery a unique postsynaptic terminal, calyx, completely covers basolateral walls of type I hair cells and receives input from multiple ribbon synapses. To date, functional role this specialized synapse remains elusive. There is limited data supporting glutamatergic transmission, K + or H accumulation in synaptic cleft as mechanisms transmission. Here transmission at calyx investigated. Whole-cell patch-clamp recordings endings were performed an vitro whole-tissue...

Type II cochlear afferents receive glutamatergic synaptic excitation from outer hair cells (OHCs) in the rat cochlea. However, it remains uncertain whether this connection is capable of providing auditory information to brain. The functional efficacy depends part on number presynaptic OHCs, their probability transmitter release, and effective electrical distance for spatial summation type fiber. present work addresses these questions using whole-cell recordings spiral process that run below...

Lateral olivocochlear (LOC) efferent neurons modulate auditory nerve fiber (ANF) activity using a large repertoire of neurotransmitters, including dopamine (DA) and acetylcholine (ACh). Little is known about how individual neurotransmitter systems are differentially utilized in response to the ever-changing acoustic environment. Here we present quantitative evidence rodents that dopaminergic LOC input ANFs dynamically regulated according animal’s recent experience. Sound exposure upregulates...

Auditory nerve fibers (ANFs) exhibit a range of spontaneous firing rates (SRs) that are inversely correlated with threshold for sounds. To probe the underlying mechanisms and time course SR differentiation during cochlear maturation, loose-patch extracellular recordings were made from ANF dendrites using acutely excised rat preparations different ages after hearing onset. Diversification SRs occurred mostly between second third postnatal week. Statistical properties spike trains showed...

Transcripts for α9 and α10 nicotinic acetylcholine receptor (nAChR) subunits are found in diverse tissues. The function of α9α10 nAChRs is best known mechanosensory cochlear hair cells, but elsewhere their roles less well understood. have been implicated as analgesic targets α-conotoxins that block produce analgesia. However, some these peptides show large potency differences between species. Additionally several studies indicated conotoxins may also activate GABAB receptors (GABABRs). To...

Inward-rectifier, G-protein-regulated and ATP-dependent K+ channels form a novel gene family of related proteins which share two transmembrane segments as common structural feature. These are only distantly to the voltage-gated Shaker-type comprising six segments. Although quaternary structure has been extensively studied in past, little is known about subunit assembly inward-rectifier channels. Differential sensitivity voltage-dependent pore block by spermine was used analyse assembly. It...