Vesicular glutamate transporter 3 is strongly upregulated in cochlear inner hair cells and spiral ganglion cells of developing circling mice

Lee, Young‐Eun; Kim, Hak Rim; Ahn, Seung Cheol

doi:10.1016/j.neulet.2014.10.053

Cited by 6 publications

(6 citation statements)

References 21 publications

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“…As described above, RA signals are crucial for the specification and differentiation of glutamatergic V3 neurons in the ventral spinal cord, where they suppress serotonin neurotransmitter phenotypes by up-regulation of neurog3 and Notch-mediated inhibition of ascl1 (Carcagno et al, 2014;Jacob et al, 2013). In cell culture studies, RA was further shown to promote glutamatergic sensory cell fates (Martinez-Monedero et al, 2008;Urban et al, 2015;Yu et al, 2015), which is particularly interesting, since RA signaling has been implicated in the development and regeneration of sensory hair cells in the inner ear that use glutamate as a major neurotransmitter (Lee et al, 2015;Romand et al, 2006;Rubbini et al, 2015;Thiede et al, 2014). However, it is currently unknown if RA signaling can also affect the induction and/or functioning of glutamatergic neurotransmitter systems in a non-permissive manner.…”

Section: Glutamate and Gabaergic Neuronsmentioning

confidence: 99%

New Insights Into the Roles of Retinoic Acid Signaling in Nervous System Development and the Establishment of Neurotransmitter Systems

Zieger

Schubert

2017

International Review of Cell and Molecular Biology

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Section: Glutamate and Gabaergic Neuronsmentioning

confidence: 99%

New Insights Into the Roles of Retinoic Acid Signaling in Nervous System Development and the Establishment of Neurotransmitter Systems

Zieger

Schubert

2017

International Review of Cell and Molecular Biology

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“…In GC-B WT mice VAMP2 staining below IHCs was significantly reduced ( Figure 4D , n = 9, p < 0.001) as shown exemplarily for a midbasal cochlear turn ( Figure 4A ) and three additional GC-B WT and GC-B KO mice ( Supplementary Figures 1A,B ). Co-staining with the vesicular glutamate transporter 3 (vGlut3), the protein that is essential for hearing ( Ruel et al, 2008 ; Seal et al, 2008 ) and changes in expression upon IHC disturbance ( Lee et al, 2015 ; Yu et al, 2016 ) revealed no difference in vGlut3 staining between GC-B WT and GC-B KO mice, while non-overlapping VAMP2 as shown at two different section levels of the IHCs was strongly reduced below IHCs of GC-B KO mice ( Figures 4B,C ). Also on the OHC level VAMP2 was significantly reduced as shown exemplarily for two different GC-B WT and GC-B KO mice ( Figure 4E ) and quantified across the cochlea ( Figure 4G , n = 8, p < 0.001).…”

Section: Resultsmentioning

confidence: 99%

“…Normal number of CtBP2/Ribeye-positive particles in ribbon synapses, previously shown to be essential for maintaining a residential vesicle pool ( Becker et al, 2018 ), afferent fiber activity and timing at stimulus onset ( Sheets et al, 2017 ) may suggest that the observed retrocochlear changes observed in GC-B KO mice may not be associated to IHC synapse deficits. Also, vGlut3 is essential for hearing ( Ruel et al, 2008 ; Seal et al, 2008 ) and its protein expression level is highly sensitive for any IHCs disturbance as shown in various studies ( Lee et al, 2015 ; Yu et al, 2016 ). Thus, the observation that vGlut3 staining between GC-B WT and GC-B KO mice, despite profound differences in the level of, e.g., the efferent marker protein VAMP2 under the same condition ( Figure 4B ), further strengthened that GC-B KO AN activity differences may unlikely be linked to deficits of IHC synapses.…”

Section: Discussionmentioning

confidence: 99%

GC-B Deficient Mice With Axon Bifurcation Loss Exhibit Compromised Auditory Processing

Wolter

Möhrle

Schmidt

et al. 2018

Front. Neural Circuits

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Sensory axon T-like branching (bifurcation) in neurons from dorsal root ganglia and cranial sensory ganglia depends on the molecular signaling cascade involving the secreted factor C-type natriuretic peptide, the natriuretic peptide receptor guanylyl cyclase B (GC-B; also known as Npr2) and cGMP-dependent protein kinase I (cGKI, also known as PKGI). The bifurcation of cranial nerves is suggested to be important for information processing by second-order neurons in the hindbrain or spinal cord. Indeed, mice with a spontaneous GC-B loss of function mutation (Npr2cn/cn) display an impaired bifurcation of auditory nerve (AN) fibers. However, these mice did not show any obvious sign of impaired basal hearing. Here, we demonstrate that mice with a targeted inactivation of the GC-B gene (Npr2lacZ/lacZ, GC-B KO mice) show an elevation of audiometric thresholds. In the inner ear, the cochlear hair cells in GC-B KO mice were nevertheless similar to those from wild type mice, justified by the typical expression of functionally relevant marker proteins. However, efferent cholinergic feedback to inner and outer hair cells was reduced in GC-B KO mice, linked to very likely reduced rapid efferent feedback. Sound-evoked AN responses of GC-B KO mice were elevated, a feature that is known to occur when the efferent axo-dendritic feedback on AN is compromised. Furthermore, late sound-evoked brainstem responses were significantly delayed in GC-B KO mice. This delay in sound response was accompanied by a weaker sensitivity of the auditory steady state response to amplitude-modulated sound stimuli. Finally, the acoustic startle response (ASR) – one of the fastest auditory responses – and the prepulse inhibition of the ASR indicated significant changes in temporal precision of auditory processing. These findings suggest that GC-B-controlled axon bifurcation of spiral ganglion neurons is important for proper activation of second-order neurons in the hindbrain and is a prerequisite for proper temporal auditory processing likely by establishing accurate efferent top-down control circuits. These data hypothesize that the bifurcation pattern of cranial nerves is important to shape spatial and temporal information processing for sensory feedback control.

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“…Glutamate receptors are involved in the hearing function (Seal and Edwards, 2006; Obholzer et al, 2008; Lee et al, 2015; Münster-Wandowski et al, 2016). Congenital deafness is also observed in mice models that lack a vesicular glutamate transporter-3 (VGLUT3).…”

Section: Gene Therapymentioning

confidence: 99%

Recent Advancements in the Regeneration of Auditory Hair Cells and Hearing Restoration

Mittal

Nguyen

Patel

et al. 2017

Front. Mol. Neurosci.

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Neurosensory responses of hearing and balance are mediated by receptors in specialized neuroepithelial sensory cells. Any disruption of the biochemical and molecular pathways that facilitate these responses can result in severe deficits, including hearing loss and vestibular dysfunction. Hearing is affected by both environmental and genetic factors, with impairment of auditory function being the most common neurosensory disorder affecting 1 in 500 newborns, as well as having an impact on the majority of elderly population. Damage to auditory sensory cells is not reversible, and if sufficient damage and cell death have taken place, the resultant deficit may lead to permanent deafness. Cochlear implants are considered to be one of the most successful and consistent treatments for deaf patients, but only offer limited recovery at the expense of loss of residual hearing. Recently there has been an increased interest in the auditory research community to explore the regeneration of mammalian auditory hair cells and restoration of their function. In this review article, we examine a variety of recent therapies, including genetic, stem cell and molecular therapies as well as discussing progress being made in genome editing strategies as applied to the restoration of hearing function.

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Vesicular glutamate transporter 3 is strongly upregulated in cochlear inner hair cells and spiral ganglion cells of developing circling mice

Cited by 6 publications

References 21 publications

New Insights Into the Roles of Retinoic Acid Signaling in Nervous System Development and the Establishment of Neurotransmitter Systems

New Insights Into the Roles of Retinoic Acid Signaling in Nervous System Development and the Establishment of Neurotransmitter Systems

GC-B Deficient Mice With Axon Bifurcation Loss Exhibit Compromised Auditory Processing

Recent Advancements in the Regeneration of Auditory Hair Cells and Hearing Restoration

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