Mouse Spiral Ganglion Neurons Research Articles

Optical measurement of glutamate release robustly reports short-term plasticity at a fast central synapse.

Recently developed fluorescent neurotransmitter indicators have enabled direct measurements of neurotransmitter in the synaptic cleft. Precise optical measurements of neurotransmitter release may be used to make inferences about presynaptic function independent of electrophysiological measurements. Here, we express iGluSnFR, a genetically encoded glutamate reporter in mouse spiral ganglion neurons to compare electrophysiological and optical readouts of presynaptic function and short-term synaptic plasticity at the endbulb of Held synapse. We show iGluSnFR robustly and approximately linearly reports glutamate release from the endbulb of Held during synaptic transmission and allows assessment of short-term plasticity during high-frequency train stimuli. Furthermore, we show that iGluSnFR expression slightly alters the time course of spontaneous postsynaptic currents, but is unlikely to impact measurements of evoked synchronous release of many synaptic vesicles. We conclude that monitoring glutamate with optical sensors at fast and large central synapses like the endbulb of Held is feasible and allows robust quantification of some, but not all aspects of glutamate release.

Thyroid hormone controls the timing of cochlear ribbon synapse maturation

Ribbon synapses in the cochlear hair cells are subject to extensive pruning and maturation processes before hearing onset. Previous studies have highlighted the pivotal role of thyroid hormone (TH) in this developmental process, yet the detailed mechanisms are largely unknown. In this study, we found that the thyroid hormone receptor α (Thrα) is expressed in both sensory epithelium and spiral ganglion neurons in mice. Hypothyroidism, induced by Pax8 gene knockout, significantly delays the synaptic pruning during postnatal development in mice. Detailed spatiotemporal analysis of ribbon synapse distribution reveals that synaptic maturation involves not only ribbon pruning but also their migration, both of which are notably delayed in the cochlea of Pax8 knockout mice. Intriguingly, postnatal hyperthyroidism, induced by intraperitoneal injections of liothyronine sodium (T3), accelerates the pruning of ribbon synapses to the mature state without affecting the auditory functions. Our findings suggest that thyroid hormone does not play a deterministic role but rather controls the timing of cochlear ribbon synapse maturation.

Berberine protects against neomycin-induced ototoxicity by reducing ROS generation and activating the PI3K/AKT pathway

In mammals, aminoglycoside antibiotic-induced injury to hair cells (HCs) and associated spiral ganglion neurons (SGNs) is irreversible and eventually leads to permanent hearing loss. Efforts have been directed towards the advancement of efficacious therapeutic treatments to protect hearing loss, but the ideal substance for treating the damaged cochlear sensory epithelium has yet to be identified. Berberine (BBR), a quaternary ammonium hydroxide extracted from Coptis chinensis, has been found to display potential anti-oxidant and neuroprotective properties. However, its involvement in aminoglycoside antibiotic-induced ototoxicity has yet to be explored or assessed. In the present study, we explored the possible anti-oxidative properties of BBR in mitigating neomycin-triggered ototoxicity. An improved survival of HCs and SGN nerve fibers (NFs) in organ of Corti (OC) explants after neomycin with BBR co-treatment was observed, and BBR treatment attenuated reactive oxygen species (ROS) generation and reduced cleaved caspase-3 signaling by activating six phosphatidylinositol 3-kinase/protein kinase B (PI3K/AKT) signaling relative subtypes, and the addition of PI3K/AKT suppressor LY294002 resulted in a decrease in the protective effect. The protective effect of BBR against ototoxicity was also evident in a neomycin-injured animal model, as evidenced by the preservation of HC and SGN in mice administered subcutaneous BBR for 7 days. In summary, all results suggest that BBR has potential as a new and effective otoprotective agent, operating via the PI3K/AKT signaling pathway.

Considering the protective effect of exendin-4 against oxidative stress in spiral ganglion neurons.

The protection of spiral ganglion neurons (SGNs) is crucial for hearing loss. Exendin-4 has been shown to have neuroprotective effects in several neurological disorders. Therefore, this study aimed to investigate the effect of the glucagon-like protein-1 receptor (GLP-1R) agonist exendin-4 on kanamycin-induced injury in mouse SGNs in vitro. In this study, GLP-1R expression in SGNs was verified by immunofluorescence and immunohistochemical staining. In vitro-cultured SGNs and the organ of Corti were exposed to kanamycin with or without exendin-4 treatment. The cell survival rate was measured using the cell counting kit-8 assay, and the damage to auditory nerve fibers (ANF) projecting radially from the SGNs was evaluated using immunofluorescence staining. Reactive oxygen species (ROS) content was determined by flow cytometry, and glutathione peroxidase (GSH-Px) content, superoxide dismutase (SOD) activity, and malondialdehyde (MDA) content were determined by spectrophotometry. Protein expression of nuclear factor erythroid-2-related factor 2/heme oxygenase-1 (Nrf2/HO-1) was detected using western blotting. GLP-1R was expressed in SGNs. Treatment with 1 mM kanamycin for 24 hr induced SGN damage. Exendin-4 (100 nM) had a protective effect against kanamycin-induced SGN cell injury, improved cell survival rate, reduced nerve fiber injury, increased SOD activity and GSH-Px level, and reduced MDA and ROS contents. The Nrf2/HO-1 pathway was activated. Exendin-4 alleviates oxidative damage and exerts neuroprotective effects in kanamycin-induced SGN injury through the Nrf2/HO-1 signaling pathway. Exendin-4 has the potential to prevent or treat hearing loss due to SGN damage.

TNN is first linked to auditory neuropathy

Autosomal recessive nonsyndromic auditory neuropathy is attributed to a genetic etiology. We identified a compound heterozygous missense variant, c.G736A (p.G246S) and c.C2954T (p.T985 M) in TNN of affected patients in a pedigree via candidate gene screening and exome sequencing. To determine the genetic etiology of deafness in the pedigree with a heterozygous missense variant in the gene TNN encoding tenascin-W associated with autosomal recessive nonsyndromic auditory neuropathy, the cochlear expression of tenascin-W was evaluated at mRNA and protein levels in mice, and Tnn knock out mice were generated and utilized to study the function of Tnn in the auditory system. Immunofluorescence stainings showed that tenascin-W was mainly expressed in the somatic cytoplasm of spiral ganglion neurons of mice. Homozygous Tnn knockout was lethal in mice, whereas Tnn heterozygous mice showed decreases in spiral ganglion neuron density and progressive hearing loss. We demonstrate that tenascin-W is expressed in the murine cochleae and is essential for the development of spiral ganglion neurons. An abnormal expression of tenascin-W can influence the development and function of SGNs and affect the function of the auditory system.

Utility of red-light ultrafast optogenetic stimulation of the auditory pathway.

Optogenetic stimulation of spiral ganglion neurons (SGNs) in the ear provides a future alternative to electrical stimulation used in current cochlear implants. Here, we employed fast and very fast variants of the red‐light‐activated channelrhodopsin (ChR) Chrimson (f‐Chrimson and vf‐Chrimson) to study their utility for optogenetic stimulation of SGNs in mice. The light requirements were higher for vf‐Chrimson than for f‐Chrimson, even when optimizing membrane expression of vf‐Chrimson by adding potassium channel trafficking sequences. Optogenetic time and intensity coding by single putative SGNs were compared with coding of acoustic clicks. vf‐Chrimson enabled putative SGNs to fire at near‐physiological rates with good temporal precision up to 250 Hz of stimulation. The dynamic range of SGN spike rate coding upon optogenetic stimulation was narrower than for acoustic clicks but larger than reported for electrical stimulation. The dynamic range of spike timing, on the other hand, was more comparable for optogenetic and acoustic stimulation. In conclusion, f‐Chrimson and vf‐Chrimson are promising candidates for optogenetic stimulation of SGNs in auditory research and future cochlear implants.

Comprehensive transcriptome analysis of cochlear spiral ganglion neurons at multiple ages.

Inner ear cochlear spiral ganglion neurons (SGNs) transmit sound information to the brainstem. Recent single cell RNA-Seq studies have revealed heterogeneities within SGNs. Nonetheless, much remains unknown about the transcriptome of SGNs, especially which genes are specifically expressed in SGNs. To address these questions, we needed a deeper and broader gene coverage than that in previous studies. We performed bulk RNA-Seq on mouse SGNs at five ages, and on two reference cell types (hair cells and glia). Their transcriptome comparison identified genes previously unknown to be specifically expressed in SGNs. To validate our dataset and provide useful genetic tools for this research field, we generated two knockin mouse strains: Scrt2-P2A-tdTomato and Celf4-3xHA-P2A-iCreER-T2A-EGFP. Our comprehensive analysis confirmed the SGN-selective expression of the candidate genes, testifying to the quality of our transcriptome data. These two mouse strains can be used to temporally label SGNs or to sort them.

Pou4f1 Defines a Subgroup of Type I Spiral Ganglion Neurons and Is Necessary for Normal Inner Hair Cell Presynaptic Ca2+ Signaling.

Acoustic signals are relayed from the ear to the brain via spiral ganglion neurons (SGNs) that receive auditory information from the cochlear inner hair cells (IHCs) and transmit that information to the cochlear nucleus of the brainstem. Physiologically distinct classes of SGNs have been characterized by their spontaneous firing rate and responses to sound and those physiological distinctions are thought to correspond to stereotyped synaptic positions on the IHC. More recently, single-cell profiling has identified multiple groups of SGNs based on transcriptional profiling; however, correlations between any of these groups and distinct neuronal physiology have not been determined. In this study, we show that expression of the POU (Pit-Oct-Unc) transcription factor Pou4f1 in type I SGNs in mice of both sexes correlates with a synaptic location on the modiolar side of IHCs. Conditional deletion of Pou4f1 in SGNs beginning in mice at embryonic day 13 rescues the early path-finding and apoptotic phenotypes reported for germline deletion of Pou4f1, resulting in a phenotypically normal development of SGN patterning. However, conditional deletion of Pou4f1 in SGNs alters the activation of Ca2+ channels in IHCs primarily by increasing their voltage sensitivity. Moreover, the modiolar to pillar gradient of active zone Ca2+ influx strength is eliminated. These results demonstrate that a subset of modiolar-targeted SGNs retain expression of Pou4f1 beyond the onset of hearing and suggest that this transcription factor plays an instructive role in presynaptic Ca2+ signaling in IHCs.SIGNIFICANCE STATEMENT Physiologically distinct classes of type I spiral ganglion neurons (SGNs) are necessary to encode sound intensities spanning the audible range. Although anatomical studies have demonstrated structural correlates for some physiologically defined classes of type I SGNs, an understanding of the molecular pathways that specify each type is only now emerging. Here, we demonstrate that expression of the transcription factor Pou4f1 corresponds to a distinct subgroup of type I SGNs that synapse on the modiolar side of inner hair cells. The conditional deletion of Pou4f1 after SGN formation does not disrupt ganglion size or morphology, change the distribution of IHC synaptic locations, or affect the creation of synapses, but it does influence the voltage dependence and strength of Ca2+ influx at presynaptic active zones in inner hair cells.

Distribution of Tryptophan Hydroxylase Immunoreactivity in the Spiral Ganglion Neurons of Mouse Cochlea.

Serotonin, also known as 5-hydroxytryptamine, is an important neurotransmitter and neuromodulator in the nervous system. Spiral ganglion neurons (SGNs) are the first station of the peripheral afferent auditory nervous system. We have previously demonstrated positive serotonin immunoreactivity in mouse SGNs. Whether serotonin in the SGNs is absorbed from the circumstances, or is synthesized by the neurons themselves is unknown. The purpose of this study was to find out the source of serotonin in the SGNs. Tryptophan hydroxylase is the rate-limiting enzyme in the process of serotonin biosynthesis. We detected tryptophan hydroxylase in the mouse SGNs using immunohistochemistry. The positive immunostaining of tryptophan hydroxylase was observed in the cytoplasm of SGNs. The cytoplasm of the SGNs was not get stained in the negative control group. Our results suggest that SGNs can synthesize serotonin themselves, and they may serve as an additional source of serotonin in the cochlea. The SGNs are serotonergic neurons. The receptors of serotonin on the membrane of SGNs interact with serotonin as auto-receptors. Serotonin in these neurons plays its physiological role in an autocrine/paracrine way.

CaBP1 regulates Cav1 L-type Ca2+ channels and their coupling to neurite growth and gene transcription in mouse spiral ganglion neurons

CaBP1 is a Ca2+ binding protein that is widely expressed in neurons in the brain, retina, and cochlea. In heterologous expression systems, CaBP1 interacts with and regulates voltage-gated Cav Ca2+ channels but whether this is the case in neurons is unknown. Here, we investigated the cellular functions of CaBP1 in cochlear spiral ganglion neurons (SGNs), which express high levels of CaBP1. Consistent with the role of CaBP1 as a suppressor of Ca2+-dependent inactivation (CDI) of Cav1 (L-type) channels, Cav1 currents underwent greater CDI in SGNs from mice lacking CaBP1 (C-KO) than in wild-type (WT) SGNs. The coupling of Cav1 channels to downstream signaling pathways was also disrupted in C-KO SGNs. Activity-dependent repression of neurite growth was significantly blunted and unresponsive to Cav1 antagonists in C-KO SGNs in contrast to WT SGNs. Moreover, Cav1-mediated Ca2+ signals and phosphorylation of cAMP-response element binding protein were reduced in C-KO SGNs compared to WT SGNs. Our findings establish a role for CaBP1 as an essential regulator of Cav1 channels in SGNs and their coupling to downstream pathways controlling activity-dependent transcription and neurite growth.

Auditory Neuropathy after Damage to Cochlear Spiral Ganglion Neurons in Mice Resulting from Conditional Expression of Diphtheria Toxin Receptors

Auditory neuropathy (AN) is a hearing disorder characterized by normal cochlear amplification to sound but poor temporal processing and auditory perception in noisy backgrounds. These deficits likely result from impairments in auditory neural synchrony; such dyssynchrony of the neural responses has been linked to demyelination of auditory nerve fibers. However, no appropriate animal models are currently available that mimic this pathology. In this study, Cre-inducible diphtheria toxin receptor (iDTR+/+) mice were cross-mated with mice containing Cre (Bhlhb5-Cre+/−) specific to spiral ganglion neurons (SGNs). In double-positive offspring mice, the injection of diphtheria toxin (DT) led to a 30–40% rate of death for SGNs, but no hair cell damage. Demyelination types of pathologies were observed around the surviving SGNs and their fibers, many of which were distorted in shape. Correspondingly, a significant reduction in response synchrony to amplitude modulation was observed in this group of animals compared to the controls, which had a Cre− genotype. Taken together, our results suggest that SGN damage following the injection of DT in mice with Bhlhb5-Cre+/− and iDTR+/− is likely to be a good AN model of demyelination.

Concomitant differentiation of a population of mouse embryonic stem cells into neuron-like cells and schwann cell-like cells in a slow-flow microfluidic device.

To send meaningful information to the brain, an inner ear cochlear implant (CI) must become closely coupled to as large and healthy a population of remaining spiral ganglion neurons (SGN) as possible. Inner ear gangliogenesis depends on macrophage migration inhibitory factor (MIF), a directionally attractant neurotrophic cytokine made by both Schwann and supporting cells (Bank et al., 2012). MIF-induced mouse embryonic stem cell (mESC)-derived "neurons" could potentially substitute for lost or damaged SGN. mESC-derived "Schwann cells" produce MIF, as do all Schwann cells (Huang et al., a; Roth et al., 2007; Roth et al., 2008) and could attract SGN to a "cell-coated" implant. Neuron- and Schwann cell-like cells were produced from a common population of mESCs in an ultra-slow-flow microfluidic device. As the populations interacted, "neurons" grew over the "Schwann cell" lawn, and early events in myelination were documented. Blocking MIF on the Schwann cell side greatly reduced directional neurite outgrowth. MIF-expressing "Schwann cells" were used to coat a CI: Mouse SGN and MIF-induced "neurons" grew directionally to the CI and to a wild-type but not MIF-knockout organ of Corti explant. Two novel stem cell-based approaches for treating the problem of sensorineural hearing loss are described. Developmental Dynamics 246:7-27, 2017. © 2016 Wiley Periodicals, Inc.

Dynamic changes in hair cell ribbon synapse induced by loss of spiral ganglion neurons in mice

Background Previous studies have suggested that primary degeneration of hair cells causes secondary degeneration of spiral ganglion neurons (SGNs), but the effect of SGN degeneration on hair cells has not been studied. In the adult mouse inner ear ouabain can selectively and permanently induce the degeneration of type 1 SGNs while leaving type 2 SGNs, efferent fibers, and sensory hair cells relatively intact. This study aimed to investigate the dynamic changes in hair cell ribbon synapse induced by loss of SGNs using ouabain application to the round window niche of adult mice. Methods In the analysis, 24 CBA/CAJ mice aged 8-10 weeks, were used, of which 6 normal mice were used as the control group. After ouabain application in the round window niche 6 times in an hour, ABR threshold shifts at least 30 dB in the three experimental groups which had six mice for 1-week group, six for 1-month group, and six for 3-month group. All 24 animals underwent function test at 1 week and then immunostaining at 1 week, 1 month, and 3 months. Results The loss of neurons was followed by degeneration of postsynaptic specializations at the afferent synapse with hair cells. One week after ouabain treatment, the nerve endings of type 1 SGNs and postsynaptic densities, as measured by Na/K ATPase and PSD-95, were affected but not entirely missing, but their partial loss had consequences for synaptic ribbons that form the presynaptic specialization at the synapse between hair cells and primary afferent neurons. Ribbon numbers in inner hair cells decreased (some of them broken and the ribbon number much decreased), and the arrangement of the synaptic ribbons had undergone a dynamic reorganization: ribbons with or without associated postsynaptic densities moved from their normal location in the basal membrane of the cell to a more apical location and the neural endings alone were also found at more apical locations without associated ribbons. After 1 month, when the neural postsynaptic densities had completed their degeneration, most ribbons were lost and the remaining ribbons had no contact with postsynaptic densities; after 3 months, the ribbon synapses were gone except for an occasional remnant of a CtBP2-positive vesicle. Hair cells were intact other than the loss of ribbons (based on immunohistochemistry and DPOAE). Conclusion These findings define the effect of SGN loss on the precise spatiotemporal size and location of ribbons and the time course of synaptic degeneration and provide a model for studying plasticity and regeneration.

Macrophage migration inhibitory factor acts as a neurotrophin in the developing inner ear

This study is the first to demonstrate that macrophage migration inhibitory factor (MIF), an immune system 'inflammatory' cytokine that is released by the developing otocyst, plays a role in regulating early innervation of the mouse and chick inner ear. We demonstrate that MIF is a major bioactive component of the previously uncharacterized otocyst-derived factor, which directs initial neurite outgrowth from the statoacoustic ganglion (SAG) to the developing inner ear. Recombinant MIF acts as a neurotrophin in promoting both SAG directional neurite outgrowth and neuronal survival and is expressed in both the developing and mature inner ear of chick and mouse. A MIF receptor, CD74, is found on both embryonic SAG neurons and adult mouse spiral ganglion neurons. Mif knockout mice are hearing impaired and demonstrate altered innervation to the organ of Corti, as well as fewer sensory hair cells. Furthermore, mouse embryonic stem cells become neuron-like when exposed to picomolar levels of MIF, suggesting the general importance of this cytokine in neural development.

Developmental Profiling of Spiral Ganglion Neurons Reveals Insights into Auditory Circuit Assembly

The sense of hearing depends on the faithful transmission of sound information from the ear to the brain by spiral ganglion (SG) neurons. However, how SG neurons develop the connections and properties that underlie auditory processing is largely unknown. We catalogued gene expression in mouse SG neurons from embryonic day 12, when SG neurons first extend projections, up until postnatal day 15, after the onset of hearing. For comparison, we also analyzed the closely related vestibular ganglion (VG). Gene ontology analysis confirmed enriched expression of genes associated with gene regulation and neurite outgrowth at early stages, with the SG and VG often expressing different members of the same gene family. At later stages, the neurons transcribe more genes related to mature function, and exhibit a dramatic increase in immune gene expression. Comparisons of the two populations revealed enhanced expression of TGFβ pathway components in SG neurons and established new markers that consistently distinguish auditory and vestibular neurons. Unexpectedly, we found that Gata3, a transcription factor commonly associated with auditory development, is also expressed in VG neurons at early stages. We therefore defined new cohorts of transcription factors and axon guidance molecules that are uniquely expressed in SG neurons and may drive auditory-specific aspects of their differentiation and wiring. We show that one of these molecules, the receptor guanylyl cyclase Npr2, is required for bifurcation of the SG central axon. Hence, our dataset provides a useful resource for uncovering the molecular basis of specific auditory circuit assembly events.

Expression and Localization of Endothelin-1 and its Receptors in the Spiral Ganglion Neurons of Mouse

Endothelin-1 (ET-1) is a peptide with various biological functions, such as vasoconstriction and cell proliferation. ET-1 was reported to be widely distributed throughout the animal body, including nervous system. The expression and localization of ET-1 and its receptors [endothelin type-A receptor (ETAR) and endothelin type-B receptor (ETBR)] in the spiral ganglion neurons have not been reported before. In this study, their presence in the mouse spiral ganglion neurons was detected at mRNA and protein levels by reverse transcription-polymerase chain reaction (RT-PCR) technique and immunohistochemistry, respectively. RT-PCR analysis indicated that ET-1, ETAR, and ETBR genes were expressed in the mouse spiral ganglion tissues. Immunohistochemical experiments demonstrated that ET-1 and ETAR were predominantly immunoreactive in the cytoplasm, while ETBR was mainly immunostained in the nucleus of the neuron bodies. The present results suggest that ET-1 may play physiological roles in the spiral ganglion cells via ETAR and ETBR.

Regional Specification of Threshold Sensitivity and Response Time in CBA/CaJ Mouse Spiral Ganglion Neurons

Previous studies of spiral ganglion neuron electrophysiology have shown that specific parameters differ according to cochlear location, with apical neurons being distinctly different from basal neurons. To align these features more precisely along the tonotopic axis of the cochlea, we developed a novel spiral ganglion culture system in which positional information is retained. Patch-clamp recordings made from neurons of known gangliotopic location revealed two basic firing pattern distributions. Membrane characteristics related to spike timing, such as accommodation, latency and onset tau, were distinctly heterogeneous, yet when averaged, they were distributed in a graded manner along the length of the cochlea. Action potential threshold levels also displayed a wide range, the averages of which were distributed nonmonotonically such that neurons with the greatest sensitivity were localized to the mid-regions of the ganglion. These studies shed new light on the complexity and sophistication of the intrinsic firing features of spiral ganglion neurons. Because timing-related elements are organized in an overall tonotopic manner, it is hypothesized that they contribute to aspects of frequency-dependent acoustic processing. On the other hand, the different distribution of threshold levels, with the greatest sensitivity in the middle region of the tonotopic map, suggests that this neuronal parameter is regulated differently and thus may contribute a distinct realm of auditory sensory processing.

Serofendic acid promotes survival of auditory hair cells and neurons of mice

Serofendic acid is a newly discovered neuroprotective substance derived from fetal calf serum. It has previously been shown to protect cortical neurons from the cytotoxicity of nitric oxide, glutamate and oxygen species. In the present study, we examined the protective effects of serofendic acid on auditory hair cells exposed to aminoglycoside toxicity using explant cultures of mouse auditory epithelia. We also determined the effect of serofendic acid on auditory neurons experiencing neurotrophin deprivation using primary cultures of mouse spiral ganglion neurons. Supplementation with serofendic acid significantly promoted the survival of auditory hair cells and neurons, and its protective effects were stronger than those of the caspase inhibitor z-VAD-fmk. These findings demonstrate the great potential of serofendic acid for protection of the auditory system.

Aspirin selectively augmented N-methyl- d-aspartate types of glutamate responses in cultured spiral ganglion neurons of mice

Aspirin is commonly used to study tinnitus in animal models because of its ability to induce tinnitus in human subjects. However, the mechanism by which aspirin affects auditory function remains unclear. To investigate the effect of aspirin on the cochlear neurotransmission, we studied its interactions with major types of membrane channels and receptors regulating the excitability of cultured type I spiral ganglion (SG) neurons. Results showed that aspirin had little effect on voltage-gated sodium and potassium currents of SG neurons. In contrast, it selectively potentiated the N-methyl- d-aspartate (NMDA) subtype of the glutamate responses in SG neurons while showing little effect on the α-amino-3-hydroxy-5-methylisozazole-4-propionic acid and kainate types of glutamate responses. The aspirin-induced current in the presence of NMDA increased in a dose-dependent manner with a half maximal concentration of 2.2 mM, and it was blocked by NMDA receptor antagonist 2-amino-5-phosphonopentanoic acid or Mg 2+. These in vitro results suggested that aspirin could interfere with the glutamatergic neurotransmission in the cochlea by selectively amplifying NMDA-mediated responses.

Dopamine modulates sodium currents in cochlear spiral ganglion neurons.

Lateral olivocochlear (LOC) efferent neurons, putatively dopaminergic, synapse on afferent dendrites of type I spiral ganglion neurons (SGNs) in the cochlea and depress their activity. To investigate the underlying mechanisms, whole-cell patch clamp recordings were obtained from mouse SGNs. Dopamine (DA), and D1-like (D1, D5) and D2-like (D2, D3 and D4) receptor agonists, reduced AP amplitude and induced a slow transient depolarization. Under voltage clamp, D1-like and D2-like agonists induced a dose-dependent inward current that was reversibly blocked by their receptor antagonists. The inward current was blocked by tetrodotoxin (TTX), implicating Na+ channels. The reduction of AP amplitude and voltage-gated Na+ current by DA and DA agonists provides a mechanism for suppressing spike activity in type I afferent neurons.