Conductive Hearing Loss Has Long-Lasting Structural and Molecular Effects on Presynaptic and Postsynaptic Structures of Auditory Nerve Synapses in the Cochlear Nucleus

Clarkson, Cheryl; Antunes, Flora M.; Rubio, María E.

doi:10.1523/jneurosci.0226-16.2016

Cited by 66 publications

(71 citation statements)

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“…These AMPAR complexes contain very little GluA2 and are mainly composed of GluA3 and GluA4 subunits (Gardner et al, 1999; Petralia et al, 2000; Wang et al, 1998). Previously we reported that transient sound reduction leads to an increase of GluA3 immunogold labeling at the postsynaptic density of AN-BC synapses (Clarkson et al, 2016; Whiting et al, 2009). Based on these observations, we hypothesized that GluA3 is involved in normal auditory processing and in experience-related changes in the auditory brainstem.…”

Section: Introductionmentioning

confidence: 93%

Impaired auditory processing and altered structure of the endbulb of Held synapse in mice lacking the GluA3 subunit of AMPA receptors

et al. 2017

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AMPA glutamate receptor complexes with fast kinetics conferred by subunits like GluA3 and GluA4 are essential for temporal precision of synaptic transmission. The specific role of GluA3 in auditory processing and experience related changes in the auditory brainstem remain unknown. We investigated the role of the GluA3 in auditory processing by using wild type (WT) and GluA3 knockout (GluA3-KO) mice. We recorded auditory brainstem responses (ABR) to assess auditory function and used electron microscopy to evaluate the ultrastructure of the auditory nerve synapse on bushy cells (AN-BC synapse). Since labeling for GluA3 subunit increases on auditory nerve synapses within the cochlear nucleus in response to transient sound reduction, we investigated the role of GluA3 in experience-dependent changes in auditory processing. We induced transient sound reduction by plugging one ear and evaluated ABR threshold and peak amplitude recovery for up to 60 days after ear plug removal in WT and GluA3-KO mice. We found that the deletion of GluA3 leads to impaired auditory signaling that is reflected in decreased ABR peak amplitudes, an increased latency of peak 2, early onset hearing loss and reduced numbers and sizes of postsynaptic densities (PSDs) of AN-BC synapses. Additionally, the lack of GluA3 hampers ABR threshold recovery after transient ear plugging. We conclude that GluA3 is required for normal auditory signaling, normal ultrastructure of AN-BC synapses in the cochlear nucleus and normal experience-dependent changes in auditory processing after transient sound reduction.

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Section: Introductionmentioning

confidence: 93%

Impaired auditory processing and altered structure of the endbulb of Held synapse in mice lacking the GluA3 subunit of AMPA receptors

et al. 2017

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“…Furthermore, it was shown that prolonged visual deprivation increases visually evoked V1 responses during the visual critical period 10 . However, evidence for homeostatic synaptic scaling in primary auditory cortex and its effects on cortical responsiveness following auditory deprivation is rare.Previously, two models for induction of an auditory deprivation have been used, sensorineural hearing loss (SNHL) [11][12][13] and conductive hearing loss (CHL) [14][15][16][17] . Whereas SNHL removes both sensory evoked activity and spontaneous activity arising from the organ of Corti 3 , CHL only reduces sound transmission to the inner ear without affecting the cochlea, reflecting a milder form of hearing loss 11 .…”

mentioning

confidence: 99%

“…Previously, two models for induction of an auditory deprivation have been used, sensorineural hearing loss (SNHL) [11][12][13] and conductive hearing loss (CHL) [14][15][16][17] . Whereas SNHL removes both sensory evoked activity and spontaneous activity arising from the organ of Corti 3 , CHL only reduces sound transmission to the inner ear without affecting the cochlea, reflecting a milder form of hearing loss 11 .…”

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confidence: 99%

“…Whereas SNHL removes both sensory evoked activity and spontaneous activity arising from the organ of Corti 3 , CHL only reduces sound transmission to the inner ear without affecting the cochlea, reflecting a milder form of hearing loss 11 . CHL is of great clinical relevance, since it represents the second most common form of hearing loss 17,18 and affects individuals across all ages 19,20 . Recent studies investigated the effects of CHL on early processing structures of the auditory pathway [16][17][18]21 or on developing auditory cortex 11,15,22,23 .…”

mentioning

confidence: 99%

“…CHL is of great clinical relevance, since it represents the second most common form of hearing loss 17,18 and affects individuals across all ages 19,20 . Recent studies investigated the effects of CHL on early processing structures of the auditory pathway [16][17][18]21 or on developing auditory cortex 11,15,22,23 . For example, CHL upregulated subunits of AMPARs in the cochlear nucleus 17,18 , suggesting a homeostatic compensatory mechanism to a reduced afferent input, but did not provoke synaptic scaling at this early stage of auditory pathway 16 .…”

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confidence: 99%

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Homeostatic plasticity and synaptic scaling in the adult mouse auditory cortex

Teichert¹,

Liebmann

Hübner

et al. 2017

Sci Rep

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It has been demonstrated that sensory deprivation results in homeostatic adjustments recovering neuronal activity of the deprived cortex. For example, deprived vision multiplicatively scales up mEPSC amplitudes in the primary visual cortex, commonly referred to as synaptic scaling. However, whether synaptic scaling also occurs in auditory cortex after auditory deprivation remains elusive. Using periodic intrinsic optical imaging in adult mice, we show that conductive hearing loss (CHL), initially led to a reduction of primary auditory cortex (A1) responsiveness to sounds. However, this was followed by a complete recovery of A1 activity evoked sounds above the threshold for bone conduction, 3 days after CHL. Over the same time course patch-clamp experiments in slices revealed that mEPSC amplitudes in A1 layers 2/3 pyramids scaled up multiplicatively in CHL mice. No recovery of sensory evoked A1 activation was evident in TNFα KO animals, which lack synaptic scaling. Additionally, we could show that the suppressive effect of sounds on visually evoked visual cortex activity completely recovered along with TNFα dependent A1 homeostasis in WT animals. This is the first demonstration of homeostatic multiplicative synaptic scaling in the adult A1. These findings suggest that mild hearing loss massively affects auditory processing in adult A1.Homeostatic plasticity is essential in maintaining a stable firing rate in neurons to compensate for prolonged perturbations of neuronal activity 1,2 . For example, a prolonged reduction of neuronal activity of cultured neocortical neurons generated compensatory changes returning firing levels back to control values 1 . Such homeostatic regulations are typically accompanied by an additional insertion of 2-amino-3-(3-hydroxy-5-methyl-isoxasol-4-yl) propanoic acid receptors (AMPARs) into all synapses of a neuron, leading to multiplicatively scaled up mEPSC (miniature excitatory postsynaptic currents) amplitudes or, "synaptic scaling" 2,3 . Specifically, this mechanism is described to globally increase (or decrease) the strength of each synapse of a neuron by the same factor in a multiplicative manner which allows the conservation of information stored in the synaptic weights 4 . Previous studies have demonstrated that synaptic scaling also takes place in vivo, e.g. after reduction of sensory cortex activity due to sensory deprivation. For example, visual deprivation by intraocular TTX injections, dark exposure, binocular enucleation or retinal lesions scales up AMPAR mediated mEPSC amplitudes in layers 2/3 pyramids of the primary visual cortex (V1) in juvenile and adult mice [5][6][7][8][9] . Furthermore, it was shown that prolonged visual deprivation increases visually evoked V1 responses during the visual critical period 10 . However, evidence for homeostatic synaptic scaling in primary auditory cortex and its effects on cortical responsiveness following auditory deprivation is rare.Previously, two models for induction of an auditory deprivation have been used, sensorineural hearing...

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Dynamics of the fragile X mental retardation protein correlates with cellular and synaptic properties in primary auditory neurons following afferent deprivation

Wang

Sakano

et al. 2020

J of Comparative Neurology

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Afferent activity dynamically regulates neuronal properties and connectivity in the central nervous system. The Fragile X mental retardation protein (FMRP) is an RNA-binding protein that regulates cellular and synaptic properties in an activitydependent manner. Whether and how FMRP level and localization are regulated by afferent input remains sparsely examined and how such regulation is associated with neuronal response to changes in sensory input is unknown. We characterized changes in FMRP level and localization in the chicken nucleus magnocellularis (NM), a primary cochlear nucleus, following afferent deprivation by unilateral cochlea removal. We observed rapid (within 2 hr) aggregation of FMRP immunoreactivity into large granular structures in a subset of deafferented NM neurons. Neurons that exhibited persistent FMRP aggregation at 12-24 hr eventually lost cytoplasmic Nissl substance, indicating cell death. A week later, FMRP expression in surviving neurons regained its homeostasis, with a slightly reduced immunostaining intensity and enhanced heterogeneity. Correlation analyses under the homeostatic status (7-14 days) revealed that neurons expressing relatively more FMRP had a higher capability of maintaining cell body size and ribosomal activity, as well as a better ability to detach inactive presynaptic terminals. Additionally, the intensity of an inhibitory postsynaptic protein, gephyrin, was reduced following deafferentation and was positively correlated with FMRP intensity, implicating an involvement of FMRP in synaptic dynamics in response to reduced afferent inputs. Collectively, this study demonstrates that afferent input regulates FMRP expression and localization in ways associated with multiple types of neuronal responses and synaptic rearrangements.

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Conductive Hearing Loss Has Long-Lasting Structural and Molecular Effects on Presynaptic and Postsynaptic Structures of Auditory Nerve Synapses in the Cochlear Nucleus

Cited by 66 publications

References 84 publications

Impaired auditory processing and altered structure of the endbulb of Held synapse in mice lacking the GluA3 subunit of AMPA receptors

Impaired auditory processing and altered structure of the endbulb of Held synapse in mice lacking the GluA3 subunit of AMPA receptors

Homeostatic plasticity and synaptic scaling in the adult mouse auditory cortex

Dynamics of the fragile X mental retardation protein correlates with cellular and synaptic properties in primary auditory neurons following afferent deprivation

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