The Glutamate–Aspartate Transporter GLAST Mediates Glutamate Uptake at Inner Hair Cell Afferent Synapses in the Mammalian Cochlea

Glowatzki, Elisabeth; Cheng, Ning; Hiel, Hakim; Yi, Eunyoung; Tanaka, Kohichi; Ellis‐Davies, Graham C. R.; Rothstein, Jeffrey D.; Bergles, Dwight E.

doi:10.1523/jneurosci.1545-06.2006

Cited by 83 publications

(68 citation statements)

References 38 publications

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“…Previous ultrastructural work reported NKAα1 immunoreactivity of the inner phalangeal and border cells in rat (Iwano et al 1990). These supporting cells express the glutamate transporter GLAST and are thought to remove glutamate from the extracellular space that has been released from the IHC (Furness and Lehre 1997;Hakuba et al 2000;Furness and Lawton 2003;Glowatzki et al 2006). The expression of NKAα1 in these supporting cells is not unexpected: glutamate transporters rely on sodium gradients to transport glutamate (Danbolt 2001).…”

Section: Discussionmentioning

confidence: 99%

Distribution of the Na,K-ATPase α Subunit in the Rat Spiral Ganglion and Organ of Corti

McLean

Smith

Glowatzki

et al. 2008

JARO

107

105

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Processing of sound in the cochlea involves both afferent and efferent innervation. The Na,K-ATPase (NKA) is essential for cells that maintain hyperpolarized membrane potentials and sodium and potassium concentration gradients. Heterogeneity of NKA subunit expression is one mechanism that tailors physiology to particular cellular demands. Therefore, to provide insight into molecular differences that distinguish the various innervation pathways in the cochlea, we performed a variety of double labeling experiments with antibodies against three of the α isoforms of the NKA (NKAα1-3) and markers identifying particular subsets of neurons or supporting cells in whole mount preparations of the organ of Corti and spiral ganglion. We found that the NKAα3 is abundantly expressed within the membranes of the spiral ganglion somata, the type I afferent terminals contacting the inner hair cells, and the medial efferent terminals contacting the outer hair cells. We also found expression of the NKAα1 in the supporting cells that neighbor the inner hair cells and express the glutamate transporter GLAST. These findings suggest that both the NKAα1 and NKAα3 are poised to play an essential role in the regulation of the type I afferent synapses, the medial efferent synapses, and also glutamate transport from the afferent-inner hair cell synapse.

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Section: Discussionmentioning

confidence: 99%

Distribution of the Na,K-ATPase α Subunit in the Rat Spiral Ganglion and Organ of Corti

McLean

Smith

Glowatzki

et al. 2008

JARO

107

105

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“…IBCs/IPhCs express Plp1 in the neonatal organ of Corti (35) and express glutamateaspartate transporter (GLAST) in the juvenile and adult organ of Corti (11,36). Experiments with mice carrying a Plp(eGFP) allele (37) in combination with PlpCreER T and Rosa26 DTA alleles [PlpDTA-Plp(eGFP)] showed that the eGFP + IBCs/ IPhCs surrounding IHCs are lost at P5 but reappear by P15 (Fig.…”

Section: Repopulation Of Ibcs/iphcs After Neonatal Ablation In the Mousementioning

confidence: 99%

“…IBCs and IPhCs, together with other SCs, are known to play critical roles during the development and maturation of the organ of Corti, in processes such as patterning of the epithelium, synaptogenesis, and initiation of electrical activity in auditory nerves before the onset of hearing and formation of extracellular matrices (1)(2)(3)(4)(5)(6)(7). SCs also are essential for the function of the mature organ of Corti, where they contribute to the maintenance of the reticular lamina at the apical surface of the epithelium (8), control the extracellular concentration of ions (e.g., K + ) (9, 10) and neurotransmitters (e.g., glutamate) (11), and support hair cell (HC) and auditory sensory neuron survival (5,(12)(13)(14)(15). SCs also have been proposed to regulate the effects of insults on HCs by releasing molecules that either promote (e.g., ERK1 and 2) (16) or reduce (e.g., heat shock protein 70) (17) HC death.…”

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confidence: 99%

Spontaneous regeneration of cochlear supporting cells after neonatal ablation ensures hearing in the adult mouse

Lagarde

Wan

Zhang

et al. 2014

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

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Supporting cells in the cochlea play critical roles in the development, maintenance, and function of sensory hair cells and auditory neurons. Although the loss of hair cells or auditory neurons results in sensorineural hearing loss, the consequence of supporting cell loss on auditory function is largely unknown. In this study, we specifically ablated inner border cells (IBCs) and inner phalangeal cells (IPhCs), the two types of supporting cells surrounding inner hair cells (IHCs) in mice in vivo. We demonstrate that the organ of Corti has the intrinsic capacity to replenish IBCs/IPhCs effectively during early postnatal development. Repopulation depends on the presence of hair cells and cells within the greater epithelial ridge and is independent of cell proliferation. This plastic response in the neonatal cochlea preserves neuronal survival, afferent innervation, and hearing sensitivity in adult mice. In contrast, the capacity for IBC/IPhC regeneration is lost in the mature organ of Corti, and consequently IHC survival and hearing sensitivity are impaired significantly, demonstrating that there is a critical period for the regeneration of cochlear supporting cells. Our findings indicate that the quiescent neonatal organ of Corti can replenish specific supporting cells completely after loss in vivo to guarantee mature hearing function.deafness | cell ablation | hair cell | organ of Corti | glia

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“…Specifically, supporting cells of the organ of Corti contribute to spontaneous activity of the auditory nerve prior to the onset of hearing (Tritsch et al 2007). In the mature sensory epithelia, glutamate transporters expressed by supporting cells have been implicated in the regulation of neurotransmission at the hair cell-afferent fiber synapse (Glowatzki et al 2006). There is also evidence indicating that supporting cells contribute to the long-term survival of type I spiral ganglion neurons (Stankovic et al 2004;Sugawara et al 2005).…”

Section: Introductionmentioning

confidence: 99%

Cell-Specific Inducible Gene Recombination in Postnatal Inner Ear Supporting Cells and Glia

Gómez-Casati

Murtie

Taylor

et al. 2009

JARO

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Recent studies indicate that supporting cells play important roles in inner ear development, function, and regeneration after injury, but the molecular mechanisms underlying these processes remain poorly understood. Inducible cell-specific gene recombination in supporting cells could be a powerful tool to study the roles of specific molecules in these cells. Here we tested the feasibility, effectiveness, and cell specificity of inducible Cremediated gene recombination in the postnatal inner ear using mice that express an inducible form of Cre (CreER T ) under the transcriptional control of the proteolipid protein (PLP) promoter. We assessed the pattern of tamoxifen-induced gene recombination in the inner ear using the ROSA26-LacZ reporter line, in which the β-galactosidase gene is expressed only after Cre-mediated excision of a loxP-flanked stop cassette. Recombination was detected in cochlear inner phalangeal cells, supporting cells surrounding hair cells in vestibular maculae and cristae. Recombination also occurred in Schwann cells. We also found that this CreER T line can be used to increase and decrease the levels of expression of a trophic factor, brain-derived neurotrophic factor, specifically in supporting cells. These results show that PLP/CreER T mice are a powerful tool to dissect gene function in inner ear supporting cells.

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The Glutamate–Aspartate Transporter GLAST Mediates Glutamate Uptake at Inner Hair Cell Afferent Synapses in the Mammalian Cochlea

Abstract: Ribbon synapses formed between inner hair cells (IHCs

Cited by 83 publications

References 38 publications

Distribution of the Na,K-ATPase α Subunit in the Rat Spiral Ganglion and Organ of Corti

Distribution of the Na,K-ATPase α Subunit in the Rat Spiral Ganglion and Organ of Corti

Spontaneous regeneration of cochlear supporting cells after neonatal ablation ensures hearing in the adult mouse

Cell-Specific Inducible Gene Recombination in Postnatal Inner Ear Supporting Cells and Glia

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