Two Distinct Channels Mediated by m2mAChR and α9nAChR Co-Exist in Type II Vestibular Hair Cells of Guinea Pig

Zhou, Tao; Wang, Yi; Guo, Chang-Kai; Zhang, Wenjuan; Yu, Hong; Zhang, Kun; Kong, Weijia

doi:10.3390/ijms14058818

Cited by 20 publications

(21 citation statements)

References 45 publications

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“…Changing HC holding potentials from -90 to -60 to -40 mV, resulted in the typical waveform changes from inward to biphasic to outward currents, as have been described in mammalian and non-mammalian studies (Art et al 1982;Art et al 1984;Glowatzki and Fuchs 2000) and suggests a similar relative contribution of nAChRs and SK channels to the efferent response as found before. Muscarinic AChR effects have been found in vestibular hair cells also (Jordan et al 2013;Li et al 2007;Poppi et al 2020;Zhou et al 2013), however in the study here the recorded HC synaptic activity is clearly mediated by α9-containing nAChRs as even the potentiated response to a pulse train could be mostly inhibited with strychnine, a blocker for α9-containing nAChRs. This does not exclude that additional mAChR effects on type II HCs exist.…”

Section: Conserved Efferent Mechanisms In the Vestibular And Auditorysupporting

confidence: 40%

Efferent Synaptic Transmission at the Vestibular Type II Hair Cell Synapse

Zhong

McIntosh

Sadeghi

et al. 2020

Preprint

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In the vestibular peripheral organs, type I and type II hair cells (HCs) transmit incoming signals via glutamatergic quantal transmission onto afferent nerve fibers. Additionally, type I HCs transmit via 'non-quantal' transmission to calyx afferent fibers, by accumulation of glutamate and potassium in the synaptic cleft. Vestibular efferent inputs originating in the brainstem contact type II HCs and vestibular afferents. Here, we aimed at characterizing the synaptic efferent inputs to type II HCs using electrical and optogenetic stimulation of efferent fibers combined with in vitro whole-cell patch clamp recording from type II HCs in the rodent vestibular crista. Properties of efferent synaptic currents in type II HCs were similar to those found in cochlear hair cells and mediated by activation of 9/nicotinic acetylcholine receptors (AChRs) and SK potassium channels. While efferents showed a low probability of release at low frequencies of stimulation, repetitive stimulation resulted in facilitation and increased probability of release. Notably, the membrane potential of type II HCs measured during optogenetic stimulation of efferents showed a strong hyperpolarization even in response to single pulses and was further enhanced by repetitive stimulation. Such efferent-mediated inhibition of type II HCs can provide a mechanism to adjust the contribution of signals from type I and type II HCs to vestibular nerve fibers. As a result, the relative input of type I hair cells to vestibular afferents will be strengthened, emphasizing the phasic properties of the incoming signal that are transmitted via fast non-quantal transmission. New and NoteworthyType II vestibular hair cells (HCs) receive inputs from efferent fibers originating in the brainstem. We used in vitro optogenetic and electrical stimulation of efferent fibers to study their synaptic inputs to type II HCs. Efferent inputs inhibited type II HCs, similar to cochlear efferent effects. We propose that efferent inputs adjust the contribution of signals from type I and type II HCs that report different components of the incoming signal to vestibular nerve fibers.

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Section: Conserved Efferent Mechanisms In the Vestibular And Auditorysupporting

confidence: 40%

Efferent Synaptic Transmission at the Vestibular Type II Hair Cell Synapse

Zhong

McIntosh

Sadeghi

et al. 2020

Preprint

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“…2 G ). Better recovery of the slow/indirect VOR component in type α9 −/− mice could be explained by an increase of excitatory influences to central neurons in VNs due to inactivation of efferent-mediated hyperpolarization on type II hair cells and subsequent afferent inhibition [10,12]. …”

Section: Discussionmentioning

confidence: 99%

“…Release of ACh due to EVS stimulation does act via α9/α10 nAChRs on type II hair cells, leading to Ca 2+ influx, activation of Ca 2+ -dependent potassium channels, and a rise of potassium efflux, which in turn causes hyperpolarization of type II hair cells. This hyperpolarization subsequently reduces Ca 2+ influx, mainly through action on voltage-dependent calcium channels, thereby reducing depolarization of hair cells [10,12]. …”

Section: Introductionmentioning

confidence: 99%

Contribution of vestibular efferent system alpha-9 nicotinic receptors to vestibulo-oculomotor interaction and short-term vestibular compensation after unilateral labyrinthectomy in mice

Eron

Davidovics

Santina

2015

Neuroscience Letters

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Sudden unilateral loss of vestibular afferent input causes nystagmus, ocular misalignment, postural instability and vertigo, all of which improve significantly over the first few days after injury through a process called vestibular compensation (VC). Efferent neuronal signals to the labyrinth are thought to be required for VC. To better understand efferent contributions to VC, we compared the time course of VC in wild-type (WT) mice and α9 knockout (α9−/−) mice, the latter lacking the α9 subunit of nicotinic acetylcholine receptors (nAChRs), which is thought to represent one signaling arm activated by the efferent vestibular system (EVS). Specifically, we investigated the time course of changes in the fast/direct and slow/indirect components of the angular vestibulo-ocular reflex (VOR) before and after unilateral labyrinthectomy (UL). Eye movements were recorded using infrared video oculography in darkness with the animal stationary and during sinusoidal (50 and 100°/s, 0.5–5 Hz) and velocity step (150°/s for 7–10 s, peak acceleration 3000°/s2) passive whole-body rotations about an Earth-vertical axis. Eye movements were measured before and 0.5, 2, 4, 6 and 9 days after UL. Before UL, we found frequency- and velocity-dependent differences between WT and α9−/− mice in generation of VOR quick phases. The VOR slow phase time constant (TC) during velocity steps, which quantifies contributions of the indirect component of the VOR, was longer in α9−/− mutants relative to WT mice. After UL, spontaneous nystagmus (SN) was suppressed significantly earlier in WT mice than in α9−/− mice, but mutants achieved greater recovery of TC symmetry and VOR quick phases. These data suggest (1) there are significant differences in vestibular and oculomotor functions between these two types of mice, and (2) efferent signals mediated by α9 nicotinic AChRs play a role during VC after UL.

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“…Each efferent axon branches profusely in the vestibular neuroepithelium (Purcell and Perachio, 1997) to innervate Type II hair cells and afferent boutons and calyx terminals (Goldberg et al, 1990a). Recent studies have shown that cochlear and vestibular hair cells express ␣9␣10 AChR (Hiel et al, 1996;Katz et al, 2004) that has an inhibitory effect (Glowatzki and Fuchs, 2000;Wersinger and Fuchs, 2011;Zhou et al, 2013;Poppi et al, 2018). On the other hand, calyx terminals express excitatory ␣4␤2 or ␣6␤2 AChR (Holt et al, 2015).…”

Section: Introductionmentioning

confidence: 99%

Efferent Inputs Are Required for Normal Function of Vestibular Nerve Afferents

2019

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A group of vestibular afferent nerve fibers with irregular-firing resting discharges are thought to play a prominent role in responses to fast head movements and vestibular plasticity. We show that, in C57BL/6 mice (either sex, 4-5 weeks old), normal activity in the efferent vestibular pathway is required for function of these irregular afferents. Thermal inhibition of efferent fibers results in a profound inhibition of irregular afferents' resting discharges, rendering them inadequate for signaling head movements. In this way, efferent inputs adjust the contribution of the peripheral irregular afferent pathway that plays a critical role in peripheral vestibular signaling and plasticity.

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Two Distinct Channels Mediated by m2mAChR and α9nAChR Co-Exist in Type II Vestibular Hair Cells of Guinea Pig

Cited by 20 publications

References 45 publications

Efferent Synaptic Transmission at the Vestibular Type II Hair Cell Synapse

Efferent Synaptic Transmission at the Vestibular Type II Hair Cell Synapse

Contribution of vestibular efferent system alpha-9 nicotinic receptors to vestibulo-oculomotor interaction and short-term vestibular compensation after unilateral labyrinthectomy in mice

Efferent Inputs Are Required for Normal Function of Vestibular Nerve Afferents

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