Onset of Cholinergic Efferent Synaptic Function in Sensory Hair Cells of the Rat Cochlea

Roux, Isabelle; Wersinger, Eric; McIntosh, J. Michael; Fuchs, Paul; Glowatzki, Elisabeth

doi:10.1523/jneurosci.2743-11.2011

Cited by 67 publications

(84 citation statements)

References 82 publications

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“…Consistent with a previous study (8), the robust increase in AP firing frequency after the application of α9α10 nicotinic receptor inhibitors (19)(20)(21) suggests that acetylcholine release from the efferent terminals, which transiently innervate the hair cells during development, controls IHC firing and membrane potential (8,15). Along this line, the α9α10 nicotinic receptor expression is upregulated, and the coupling between α9α10 and SK2 potassium channels tightens up during the first postnatal week (8,28,29). However, the low frequency of the inhibitory postsynaptic potentials would not be sufficient to account for the long hyperpolarization period seen in our recordings (30).…”

Section: Discussionsupporting

confidence: 82%

Spatiotemporal pattern of action potential firing in developing inner hair cells of the mouse cochlea

Sendin

Bourien

Rassendren

et al. 2014

Proc. Natl. Acad. Sci. U.S.A.

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Inner hair cells (IHCs) are the primary transducer for sound encoding in the cochlea. In contrast to the graded receptor potential of adult IHCs, immature hair cells fire spontaneous calcium action potentials during the first postnatal week. This spiking activity has been proposed to shape the tonotopic map along the ascending auditory pathway. Using perforated patch-clamp recordings, we show that developing IHCs fire spontaneous bursts of action potentials and that this pattern is indistinguishable along the basoapical gradient of the developing cochlea. In both apical and basal IHCs, the spiking behavior undergoes developmental changes, where the bursts of action potential tend to occur at a regular time interval and have a similar length toward the end of the first postnatal week. Although disruption of purinergic signaling does not interfere with the action potential firing pattern, pharmacological ablation of the α9α10 nicotinic receptor elicits an increase in the discharge rate. We therefore suggest that in addition to carrying place information to the ascending auditory nuclei, the IHCs firing pattern controlled by the α9α10 receptor conveys a temporal signature of the cochlear development.auditory system | electrical activity | ATP receptor | acetylcholine receptor

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Section: Discussionsupporting

confidence: 82%

Spatiotemporal pattern of action potential firing in developing inner hair cells of the mouse cochlea

Sendin

Bourien

Rassendren

et al. 2014

Proc. Natl. Acad. Sci. U.S.A.

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“…Although similar to homomeric a9 nAChRs, heteromeric a9a10 nAChRs more closely resemble the pharmacological and electrophysiological properties of native nAChRs found in cochlear hair cells (Elgoyhen et al, 2001;Sgard et al, 2002;Lustig, 2006). In addition, both knockout and developmental studies indicate that responses of cochlear hair cells to ACh are mediated through a9a10 nAChRs (Vetter et al, 1999(Vetter et al, , 2007Katz et al, 2004;Roux et al, 2011).…”

Section: Introductionmentioning

confidence: 63%

Molecular Interaction of α-Conotoxin RgIA with the Rat α9α10 Nicotinic Acetylcholine Receptor

et al. 2015

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The a9a10 nicotinic acetylcholine receptor (nAChR) was first identified in the auditory system, where it mediates synaptic transmission between efferent olivocochlear cholinergic fibers and cochlea hair cells. This receptor gained further attention due to its potential role in chronic pain and breast and lung cancers. We previously showed that a-conotoxin (a-CTx) RgIA, one of the few a9a10 selective ligands identified to date, is 300-fold less potent on human versus rat a9a10 nAChR. This species difference was conferred by only one residue in the (2), rather than (1), binding region of the a9 subunit. In light of this unexpected discovery, we sought to determine other interacting residues with a-CTx RgIA. A previous molecular modeling study, based on the structure of the homologous molluscan acetylcholine-binding protein, predicted that RgIA interacts with three residues on the a9(1) face and two residues on the a10(2) face of the a9a10 nAChR. However, mutations of these residues had little or no effect on toxin block of the a9a10 nAChR. In contrast, mutations of homologous residues in the opposing nAChR subunits (a10 Ε197, P200 and a9 T61, D121) resulted in 19-to 1700-fold loss of toxin activity. Based on the crystal structure of the extracellular domain (ECD) of human a9 nAChR, we modeled the rat a9a10 ECD and its complexes with a-CTx RgIA and acetylcholine. Our data support the interaction of a-CTx RgIA at the a10/a9 rather than the a9/a10 nAChR subunit interface, and may facilitate the development of selective ligands with therapeutic potential.

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“…1C). Despite the larger size of the SK2 current in OE IHCs, its developmental time course was similar to that in control cells (8,17,21), being completely down-regulated by P16-P18 (Fig. 1C).…”

Section: +mentioning

confidence: 73%

Presynaptic maturation in auditory hair cells requires a critical period of sensory-independent spiking activity

Johnson

Kuhn

Franz

et al. 2013

Proc. Natl. Acad. Sci. U.S.A.

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The development of neural circuits relies on spontaneous electrical activity that occurs during immature stages of development. In the developing mammalian auditory system, spontaneous calcium action potentials are generated by inner hair cells (IHCs), which form the primary sensory synapse. It remains unknown whether this electrical activity is required for the functional maturation of the auditory system. We found that sensory-independent electrical activity controls synaptic maturation in IHCs. We used a mouse model in which the potassium channel SK2 is normally overexpressed, but can be modulated in vivo using doxycycline. SK2 overexpression affected the frequency and duration of spontaneous action potentials, which prevented the development of the Ca 2+ -sensitivity of vesicle fusion at IHC ribbon synapses, without affecting their morphology or general cell development. By manipulating the in vivo expression of SK2 channels, we identified the "critical period" during which spiking activity influences IHC synaptic maturation. Here we provide direct evidence that IHC development depends upon a specific temporal pattern of calcium spikes before sound-driven neuronal activity.exocytosis | cochlea | calcium current | kcnn2

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Onset of Cholinergic Efferent Synaptic Function in Sensory Hair Cells of the Rat Cochlea

Cited by 67 publications

References 82 publications

Spatiotemporal pattern of action potential firing in developing inner hair cells of the mouse cochlea

Spatiotemporal pattern of action potential firing in developing inner hair cells of the mouse cochlea

Molecular Interaction of α-Conotoxin RgIA with the Rat α9α10 Nicotinic Acetylcholine Receptor

Presynaptic maturation in auditory hair cells requires a critical period of sensory-independent spiking activity

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