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Specific synaptopathies diversify brain responses and hearing disorders: you lose the gain from early life.

Knipper M, Panford-Walsh R, Singer W, Rüttiger L, Zimmermann U - Cell Tissue Res. (2015)

Bottom Line: With sensory experience, the IHC pre- and post-synapse phenotype matures towards the instruction of low-SR, high-threshold and of high-SR, low-threshold auditory fiber characteristics.Corticosteroid feedback together with local brain-derived nerve growth factor (BDNF) and catecholaminergic neurotransmitters (dopamine) might be essential for this developmental step.In this review, we address the question of whether the control of low-SR and high-SR fiber characteristics is linked to various degrees of vulnerability of auditory fibers in the mature system.

View Article: PubMed Central - PubMed

Affiliation: Department of Otolaryngology, Head and Neck Surgery, Tübingen Hearing Research Center (THRC), Molecular Physiology of Hearing, University of Tübingen, Elfriede-Aulhorn-Straße 5, 72076, Tübingen, Germany, marlies.knipper@uni-tuebingen.de.

ABSTRACT
Before hearing onset, inner hair cell (IHC) maturation proceeds under the influence of spontaneous Ca(2+) action potentials (APs). The temporal signature of the IHC Ca(2+) AP is modified through an efferent cholinergic feedback from the medial olivocochlear bundle (MOC) and drives the IHC pre- and post-synapse phenotype towards low spontaneous (spike) rate (SR), high-threshold characteristics. With sensory experience, the IHC pre- and post-synapse phenotype matures towards the instruction of low-SR, high-threshold and of high-SR, low-threshold auditory fiber characteristics. Corticosteroid feedback together with local brain-derived nerve growth factor (BDNF) and catecholaminergic neurotransmitters (dopamine) might be essential for this developmental step. In this review, we address the question of whether the control of low-SR and high-SR fiber characteristics is linked to various degrees of vulnerability of auditory fibers in the mature system. In particular, we examine several IHC synaptopathies in the context of various hearing disorders and exemplified shortfalls before and after hearing onset.

No MeSH data available.


Related in: MedlinePlus

Association of central responsiveness and hearing disorder to various degrees of IHC neurodegeneration. Activity-dependent plasticity gene Arc/Arg3.1 expression (blue Arc/Arg3.1 mRNA, red Arc/Arg.31 protein) in individual adult female Wistar rats not exposed (control) or exposed to 80, 100, 110 and 120 dB SPL (sound pressure level) at 14 days following sound exposure. a–a’’’’ Auditory cortex. b–b’’’’ Hippocampal CA1 region. Note that Arc/Arg3.1 expression in tinnitus-free animals (No-tinnitus, 80, 100, 110 dB SPL) is gradually enhanced, whereas in tinnitus animals (TINNITUS, 120 dB SPL), no change in the expression of Arc/Arg3.1 is observed. c–c’’’’ Arc/Arg3.1 expression levels in the posterior-lateral region of the cortical amygdala, used as a control tissue, remain unaltered. d–d’’’’ Auditory brainstem response (ABR) wave functions of individual animals not exposed (control) or exposed to 80, 100, 110 and 120 dB SPL at 14 days following sound exposure (black wave in dbelow graph average ABR wave function of untreated animals). The changes in waveforms and signals were calculated as a correlation factor (CorF) as described in Singer et al. (2013). Dashed lines indicate the 95 % confidence interval for the controls. Note that auditory cortex and hippocampal Arc/Arg3.1 expression is correlated with ABR waves. e–e’’’’ Counts of IHC ribbons revealed a gradual reduction in the basal cochlear turn of animals exposed to 100, 110 and 120 dB SPL. For more information, see Singer et al. (2013). Note that auditory cortex and hippocampal Arc/Arg3.1 expression is also correlated with IHC ribbon counts of the basal cochlear turn. Interestingly, mobilized Arc/Arg3.1 levels and restored ABR waves occur despite increasing ribbon loss after exposure to 100 and 110 dB SPL sound in No-tinnitus animals. In contrast, a critical loss of IHC ribbons after 120 dB SPL noise exposure was linked with a failure to mobilize Arc/Arg3.1 and restore ABR waves in TINNITUS animals. For further details, see Singer et al. (2013)
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Fig3: Association of central responsiveness and hearing disorder to various degrees of IHC neurodegeneration. Activity-dependent plasticity gene Arc/Arg3.1 expression (blue Arc/Arg3.1 mRNA, red Arc/Arg.31 protein) in individual adult female Wistar rats not exposed (control) or exposed to 80, 100, 110 and 120 dB SPL (sound pressure level) at 14 days following sound exposure. a–a’’’’ Auditory cortex. b–b’’’’ Hippocampal CA1 region. Note that Arc/Arg3.1 expression in tinnitus-free animals (No-tinnitus, 80, 100, 110 dB SPL) is gradually enhanced, whereas in tinnitus animals (TINNITUS, 120 dB SPL), no change in the expression of Arc/Arg3.1 is observed. c–c’’’’ Arc/Arg3.1 expression levels in the posterior-lateral region of the cortical amygdala, used as a control tissue, remain unaltered. d–d’’’’ Auditory brainstem response (ABR) wave functions of individual animals not exposed (control) or exposed to 80, 100, 110 and 120 dB SPL at 14 days following sound exposure (black wave in dbelow graph average ABR wave function of untreated animals). The changes in waveforms and signals were calculated as a correlation factor (CorF) as described in Singer et al. (2013). Dashed lines indicate the 95 % confidence interval for the controls. Note that auditory cortex and hippocampal Arc/Arg3.1 expression is correlated with ABR waves. e–e’’’’ Counts of IHC ribbons revealed a gradual reduction in the basal cochlear turn of animals exposed to 100, 110 and 120 dB SPL. For more information, see Singer et al. (2013). Note that auditory cortex and hippocampal Arc/Arg3.1 expression is also correlated with IHC ribbon counts of the basal cochlear turn. Interestingly, mobilized Arc/Arg3.1 levels and restored ABR waves occur despite increasing ribbon loss after exposure to 100 and 110 dB SPL sound in No-tinnitus animals. In contrast, a critical loss of IHC ribbons after 120 dB SPL noise exposure was linked with a failure to mobilize Arc/Arg3.1 and restore ABR waves in TINNITUS animals. For further details, see Singer et al. (2013)

Mentions: Interestingly, depending on the degree of IHC deafferentation, a surprisingly divergent recovery rate of supra-threshold delayed ABR waves and central responsiveness, as measured through activity-dependent genes such as Arc/Arg3.1, can be observed in behaviorally trained animals (Fig. 2; Knipper et al. 2013; Rüttiger et al. 2013; Singer et al. 2013). Behavioral studies on rats can be performed with validated conditioning in which animals are trained to sit on a platform during silence (Fig. 2b) but to move to obtain sugar water rewards during sound (Fig. 2b’−b’’’’’’; Rüttiger et al. 2003). Arc/Arg3.1 is a cytoskeletal protein that is mobilized after long-term potentiation (LTP)-like activity to scale AMPA receptors in post-synapses up and down, a process essential for LTP consolidation. This process is also a prerequisite for long-term increases in the strength of a synapse in response to a reduced firing rate (Beique et al. 2011) or to visual deprivation (Gao et al. 2010; for reviews, see Bramham et al. 2008, 2010; Korb and Finkbeiner 2011; Tzingounis and Nicoll 2006). Accordingly, the findings in rats show that the expression levels of Arc/Arg 3.1 are gradually increased in layer II−III of the auditory cortex (Fig. 3a−a’’’) and in the hippocampal CA1 region (Fig. 3b−b’’’) at 2–3 weeks after acoustically exposing animals to 80, 100, or 110 dB SPL (sound pressure level) sound for 2 h (Singer et al. 2013), despite decreasing numbers of IHC ribbons (Fig. 3e−e’’’). Moreover, as long as Arc/Arg3.1 expression is increasingly mobilized, a successful restoration of centrally generated ABR waves (ABR wave IV) occurs (Fig. 3d−d’’’) always being correlated with No-Tinnitus (Fig. 3, No-tinnitus). When IHC ribbons are critically declined, as observed after 120 dB SPL sound exposure, Arc/Arg 3.1 mobilization drops out and central ABR waves fail to be restored and are now linked to tinnitus (Fig. 3, Tinnitus, 120 dB SPL; Singer et al. 2013). A contrasting central brain response dependent on the degree of IHC ribbon loss occurs, even among animals that are equally acoustically exposed to moderate acoustic trauma (Rüttiger et al. 2013). At 2 to 3 weeks after a moderate acoustic trauma, either a lower IHC ribbon loss is correlated with the successful restoration of ABR wave IV in animals without tinnitus or a higher degree of deafferentation and IHC ribbon loss is correlated with an inability to restore ABR wave IV with behaviorally tested tinnitus (Rüttiger et al. 2013). As seen before, animals without tinnitus exhibit higher cortical Arc/Arg3.1 expression levels than those with tinnitus (Singer et al. 2013). The vulnerability of IHC synapses to moderate acoustic trauma is enhanced when corticosteroid levels in animals are strongly elevated through a stress paradigm at the time of trauma (Singer et al. 2013).Fig. 2


Specific synaptopathies diversify brain responses and hearing disorders: you lose the gain from early life.

Knipper M, Panford-Walsh R, Singer W, Rüttiger L, Zimmermann U - Cell Tissue Res. (2015)

Association of central responsiveness and hearing disorder to various degrees of IHC neurodegeneration. Activity-dependent plasticity gene Arc/Arg3.1 expression (blue Arc/Arg3.1 mRNA, red Arc/Arg.31 protein) in individual adult female Wistar rats not exposed (control) or exposed to 80, 100, 110 and 120 dB SPL (sound pressure level) at 14 days following sound exposure. a–a’’’’ Auditory cortex. b–b’’’’ Hippocampal CA1 region. Note that Arc/Arg3.1 expression in tinnitus-free animals (No-tinnitus, 80, 100, 110 dB SPL) is gradually enhanced, whereas in tinnitus animals (TINNITUS, 120 dB SPL), no change in the expression of Arc/Arg3.1 is observed. c–c’’’’ Arc/Arg3.1 expression levels in the posterior-lateral region of the cortical amygdala, used as a control tissue, remain unaltered. d–d’’’’ Auditory brainstem response (ABR) wave functions of individual animals not exposed (control) or exposed to 80, 100, 110 and 120 dB SPL at 14 days following sound exposure (black wave in dbelow graph average ABR wave function of untreated animals). The changes in waveforms and signals were calculated as a correlation factor (CorF) as described in Singer et al. (2013). Dashed lines indicate the 95 % confidence interval for the controls. Note that auditory cortex and hippocampal Arc/Arg3.1 expression is correlated with ABR waves. e–e’’’’ Counts of IHC ribbons revealed a gradual reduction in the basal cochlear turn of animals exposed to 100, 110 and 120 dB SPL. For more information, see Singer et al. (2013). Note that auditory cortex and hippocampal Arc/Arg3.1 expression is also correlated with IHC ribbon counts of the basal cochlear turn. Interestingly, mobilized Arc/Arg3.1 levels and restored ABR waves occur despite increasing ribbon loss after exposure to 100 and 110 dB SPL sound in No-tinnitus animals. In contrast, a critical loss of IHC ribbons after 120 dB SPL noise exposure was linked with a failure to mobilize Arc/Arg3.1 and restore ABR waves in TINNITUS animals. For further details, see Singer et al. (2013)
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Fig3: Association of central responsiveness and hearing disorder to various degrees of IHC neurodegeneration. Activity-dependent plasticity gene Arc/Arg3.1 expression (blue Arc/Arg3.1 mRNA, red Arc/Arg.31 protein) in individual adult female Wistar rats not exposed (control) or exposed to 80, 100, 110 and 120 dB SPL (sound pressure level) at 14 days following sound exposure. a–a’’’’ Auditory cortex. b–b’’’’ Hippocampal CA1 region. Note that Arc/Arg3.1 expression in tinnitus-free animals (No-tinnitus, 80, 100, 110 dB SPL) is gradually enhanced, whereas in tinnitus animals (TINNITUS, 120 dB SPL), no change in the expression of Arc/Arg3.1 is observed. c–c’’’’ Arc/Arg3.1 expression levels in the posterior-lateral region of the cortical amygdala, used as a control tissue, remain unaltered. d–d’’’’ Auditory brainstem response (ABR) wave functions of individual animals not exposed (control) or exposed to 80, 100, 110 and 120 dB SPL at 14 days following sound exposure (black wave in dbelow graph average ABR wave function of untreated animals). The changes in waveforms and signals were calculated as a correlation factor (CorF) as described in Singer et al. (2013). Dashed lines indicate the 95 % confidence interval for the controls. Note that auditory cortex and hippocampal Arc/Arg3.1 expression is correlated with ABR waves. e–e’’’’ Counts of IHC ribbons revealed a gradual reduction in the basal cochlear turn of animals exposed to 100, 110 and 120 dB SPL. For more information, see Singer et al. (2013). Note that auditory cortex and hippocampal Arc/Arg3.1 expression is also correlated with IHC ribbon counts of the basal cochlear turn. Interestingly, mobilized Arc/Arg3.1 levels and restored ABR waves occur despite increasing ribbon loss after exposure to 100 and 110 dB SPL sound in No-tinnitus animals. In contrast, a critical loss of IHC ribbons after 120 dB SPL noise exposure was linked with a failure to mobilize Arc/Arg3.1 and restore ABR waves in TINNITUS animals. For further details, see Singer et al. (2013)
Mentions: Interestingly, depending on the degree of IHC deafferentation, a surprisingly divergent recovery rate of supra-threshold delayed ABR waves and central responsiveness, as measured through activity-dependent genes such as Arc/Arg3.1, can be observed in behaviorally trained animals (Fig. 2; Knipper et al. 2013; Rüttiger et al. 2013; Singer et al. 2013). Behavioral studies on rats can be performed with validated conditioning in which animals are trained to sit on a platform during silence (Fig. 2b) but to move to obtain sugar water rewards during sound (Fig. 2b’−b’’’’’’; Rüttiger et al. 2003). Arc/Arg3.1 is a cytoskeletal protein that is mobilized after long-term potentiation (LTP)-like activity to scale AMPA receptors in post-synapses up and down, a process essential for LTP consolidation. This process is also a prerequisite for long-term increases in the strength of a synapse in response to a reduced firing rate (Beique et al. 2011) or to visual deprivation (Gao et al. 2010; for reviews, see Bramham et al. 2008, 2010; Korb and Finkbeiner 2011; Tzingounis and Nicoll 2006). Accordingly, the findings in rats show that the expression levels of Arc/Arg 3.1 are gradually increased in layer II−III of the auditory cortex (Fig. 3a−a’’’) and in the hippocampal CA1 region (Fig. 3b−b’’’) at 2–3 weeks after acoustically exposing animals to 80, 100, or 110 dB SPL (sound pressure level) sound for 2 h (Singer et al. 2013), despite decreasing numbers of IHC ribbons (Fig. 3e−e’’’). Moreover, as long as Arc/Arg3.1 expression is increasingly mobilized, a successful restoration of centrally generated ABR waves (ABR wave IV) occurs (Fig. 3d−d’’’) always being correlated with No-Tinnitus (Fig. 3, No-tinnitus). When IHC ribbons are critically declined, as observed after 120 dB SPL sound exposure, Arc/Arg 3.1 mobilization drops out and central ABR waves fail to be restored and are now linked to tinnitus (Fig. 3, Tinnitus, 120 dB SPL; Singer et al. 2013). A contrasting central brain response dependent on the degree of IHC ribbon loss occurs, even among animals that are equally acoustically exposed to moderate acoustic trauma (Rüttiger et al. 2013). At 2 to 3 weeks after a moderate acoustic trauma, either a lower IHC ribbon loss is correlated with the successful restoration of ABR wave IV in animals without tinnitus or a higher degree of deafferentation and IHC ribbon loss is correlated with an inability to restore ABR wave IV with behaviorally tested tinnitus (Rüttiger et al. 2013). As seen before, animals without tinnitus exhibit higher cortical Arc/Arg3.1 expression levels than those with tinnitus (Singer et al. 2013). The vulnerability of IHC synapses to moderate acoustic trauma is enhanced when corticosteroid levels in animals are strongly elevated through a stress paradigm at the time of trauma (Singer et al. 2013).Fig. 2

Bottom Line: With sensory experience, the IHC pre- and post-synapse phenotype matures towards the instruction of low-SR, high-threshold and of high-SR, low-threshold auditory fiber characteristics.Corticosteroid feedback together with local brain-derived nerve growth factor (BDNF) and catecholaminergic neurotransmitters (dopamine) might be essential for this developmental step.In this review, we address the question of whether the control of low-SR and high-SR fiber characteristics is linked to various degrees of vulnerability of auditory fibers in the mature system.

View Article: PubMed Central - PubMed

Affiliation: Department of Otolaryngology, Head and Neck Surgery, Tübingen Hearing Research Center (THRC), Molecular Physiology of Hearing, University of Tübingen, Elfriede-Aulhorn-Straße 5, 72076, Tübingen, Germany, marlies.knipper@uni-tuebingen.de.

ABSTRACT
Before hearing onset, inner hair cell (IHC) maturation proceeds under the influence of spontaneous Ca(2+) action potentials (APs). The temporal signature of the IHC Ca(2+) AP is modified through an efferent cholinergic feedback from the medial olivocochlear bundle (MOC) and drives the IHC pre- and post-synapse phenotype towards low spontaneous (spike) rate (SR), high-threshold characteristics. With sensory experience, the IHC pre- and post-synapse phenotype matures towards the instruction of low-SR, high-threshold and of high-SR, low-threshold auditory fiber characteristics. Corticosteroid feedback together with local brain-derived nerve growth factor (BDNF) and catecholaminergic neurotransmitters (dopamine) might be essential for this developmental step. In this review, we address the question of whether the control of low-SR and high-SR fiber characteristics is linked to various degrees of vulnerability of auditory fibers in the mature system. In particular, we examine several IHC synaptopathies in the context of various hearing disorders and exemplified shortfalls before and after hearing onset.

No MeSH data available.


Related in: MedlinePlus