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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

Maturation of the inner hair cell synapse (IHC). a Prior to hearing onset, IHCs exhibit spontaneous Ca2+ action potentials (APs), which are elicited through ATP signaling ([1]). Influenced by the temporal signature provided through nicotinic acetylcholine receptor (nAChR)α9/α10-mediated axosomatic IHC input ([2]), the synaptic machinery of IHCs progressively evolves and can form low-SR (spontaneous [spike] rates), high-threshold fiber characteristics ([3]; EPSP excitatory post-synaptic potential, AF auditory fiber, AN auditory nerve, AC auditory cortex, CN cochlear nucleus, DCN dorsal cochlear nucleus, LSO lateral superior olivary nucleus, MSO medial superior olivary nucleus, MGB medial geniculate body, MNTB medial nucleus of the trapezoid body, SOC superior olivary complex, VCN ventral cochlear nucleus, IC inferior colliculus, MOC-EF medial olivocochlear efferent fibers, SK2 potassium channel). b Ca2+ APs are terminated by thyroid hormone action ([4]). After hearing onset, with sensory experience, the IHC synapse matures and high-SR fibers characteristics evolve possibly under the influence of a corticotropin-releasing hormone (CRH)/brain-derived nerve growth factor (BDNF)/dopamine signaling cascade ([5]). Low-SR fibers are preferentially lost with moderate sound and, with age, a deprivation paradigm that possibly can be centrally compensated (left). In contrast, a critical loss of high-SR fibers might lead to the obstruction of central compensation (right; BK large-conductance, voltage- and Ca2+-activated potassium channel, BLA basolateral complex of the amygdala, HPA hypothalamic-pituitary-adrenal axis, LOC-EF lateral olivocochlear efferent fiber, MR/GR glucocorticoid receptors/mineralocorticoid receptors, TGN trans-Golgi network)
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Fig1: Maturation of the inner hair cell synapse (IHC). a Prior to hearing onset, IHCs exhibit spontaneous Ca2+ action potentials (APs), which are elicited through ATP signaling ([1]). Influenced by the temporal signature provided through nicotinic acetylcholine receptor (nAChR)α9/α10-mediated axosomatic IHC input ([2]), the synaptic machinery of IHCs progressively evolves and can form low-SR (spontaneous [spike] rates), high-threshold fiber characteristics ([3]; EPSP excitatory post-synaptic potential, AF auditory fiber, AN auditory nerve, AC auditory cortex, CN cochlear nucleus, DCN dorsal cochlear nucleus, LSO lateral superior olivary nucleus, MSO medial superior olivary nucleus, MGB medial geniculate body, MNTB medial nucleus of the trapezoid body, SOC superior olivary complex, VCN ventral cochlear nucleus, IC inferior colliculus, MOC-EF medial olivocochlear efferent fibers, SK2 potassium channel). b Ca2+ APs are terminated by thyroid hormone action ([4]). After hearing onset, with sensory experience, the IHC synapse matures and high-SR fibers characteristics evolve possibly under the influence of a corticotropin-releasing hormone (CRH)/brain-derived nerve growth factor (BDNF)/dopamine signaling cascade ([5]). Low-SR fibers are preferentially lost with moderate sound and, with age, a deprivation paradigm that possibly can be centrally compensated (left). In contrast, a critical loss of high-SR fibers might lead to the obstruction of central compensation (right; BK large-conductance, voltage- and Ca2+-activated potassium channel, BLA basolateral complex of the amygdala, HPA hypothalamic-pituitary-adrenal axis, LOC-EF lateral olivocochlear efferent fiber, MR/GR glucocorticoid receptors/mineralocorticoid receptors, TGN trans-Golgi network)

Mentions: Prior to hearing onset, spontaneous Ca2+ APs of IHCs are the result of ATP that is released from the organ of Kölliker and that drives small voltage input in IHCs after birth (Tritsch and Bergles 2010; Tritsch et al. 2007; for a review, see Wang and Bergles 2014). ATP possibly activates IHCs through ligand-gated ionotropic P2X receptors or G-protein-coupled metabotropic P2Y receptors, both of which have been reported to induce increases of the intracellular Ca2+ concentration ([Ca2+]i; Harada 2010). During the period of spontaneous Ca2+ APs, the synaptic machinery of IHCs progressively evolves from multiple spherical bodies, typical of immature hair cells (Fig. 1a), to more confined active zones anchoring a single ribbon (Sobkowicz et al. 1982; Fig. 1b), namely the sub-micrometer electron-dense structures that tether synaptic vesicles (Zenisek et al. 2004). Various excellent reviews have focused on this early developmental period of the inner ear (Castellano-Munoz and Ricci 2014; Fuchs 2005; Marcotti 2012; Moser et al. 2013; Safieddine et al. 2012; Schmitz 2009). The disturbance of ATP signaling during this time has significant adverse effects on the auditory system. This has been shown by reducing ATP-dependent Ca2+ signaling activity in cochlear non-sensory cells, an effect that has been achieved by knocking down the expression of phosphatidylinositol phosphate kinase type 1γ (PIPKIγ), a key enzyme in the generation of phosphatidylinositol 4,5-bisphosphate (Rodriguez et al. 2012). PIPKIγ+/− mice have dramatically elevated hearing thresholds, particularly in response to high-frequency sound. Further studies are essential for an understanding of the profound consequences of this early event in more detail.Fig. 1


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)

Maturation of the inner hair cell synapse (IHC). a Prior to hearing onset, IHCs exhibit spontaneous Ca2+ action potentials (APs), which are elicited through ATP signaling ([1]). Influenced by the temporal signature provided through nicotinic acetylcholine receptor (nAChR)α9/α10-mediated axosomatic IHC input ([2]), the synaptic machinery of IHCs progressively evolves and can form low-SR (spontaneous [spike] rates), high-threshold fiber characteristics ([3]; EPSP excitatory post-synaptic potential, AF auditory fiber, AN auditory nerve, AC auditory cortex, CN cochlear nucleus, DCN dorsal cochlear nucleus, LSO lateral superior olivary nucleus, MSO medial superior olivary nucleus, MGB medial geniculate body, MNTB medial nucleus of the trapezoid body, SOC superior olivary complex, VCN ventral cochlear nucleus, IC inferior colliculus, MOC-EF medial olivocochlear efferent fibers, SK2 potassium channel). b Ca2+ APs are terminated by thyroid hormone action ([4]). After hearing onset, with sensory experience, the IHC synapse matures and high-SR fibers characteristics evolve possibly under the influence of a corticotropin-releasing hormone (CRH)/brain-derived nerve growth factor (BDNF)/dopamine signaling cascade ([5]). Low-SR fibers are preferentially lost with moderate sound and, with age, a deprivation paradigm that possibly can be centrally compensated (left). In contrast, a critical loss of high-SR fibers might lead to the obstruction of central compensation (right; BK large-conductance, voltage- and Ca2+-activated potassium channel, BLA basolateral complex of the amygdala, HPA hypothalamic-pituitary-adrenal axis, LOC-EF lateral olivocochlear efferent fiber, MR/GR glucocorticoid receptors/mineralocorticoid receptors, TGN trans-Golgi network)
© Copyright Policy - OpenAccess
Related In: Results  -  Collection

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Fig1: Maturation of the inner hair cell synapse (IHC). a Prior to hearing onset, IHCs exhibit spontaneous Ca2+ action potentials (APs), which are elicited through ATP signaling ([1]). Influenced by the temporal signature provided through nicotinic acetylcholine receptor (nAChR)α9/α10-mediated axosomatic IHC input ([2]), the synaptic machinery of IHCs progressively evolves and can form low-SR (spontaneous [spike] rates), high-threshold fiber characteristics ([3]; EPSP excitatory post-synaptic potential, AF auditory fiber, AN auditory nerve, AC auditory cortex, CN cochlear nucleus, DCN dorsal cochlear nucleus, LSO lateral superior olivary nucleus, MSO medial superior olivary nucleus, MGB medial geniculate body, MNTB medial nucleus of the trapezoid body, SOC superior olivary complex, VCN ventral cochlear nucleus, IC inferior colliculus, MOC-EF medial olivocochlear efferent fibers, SK2 potassium channel). b Ca2+ APs are terminated by thyroid hormone action ([4]). After hearing onset, with sensory experience, the IHC synapse matures and high-SR fibers characteristics evolve possibly under the influence of a corticotropin-releasing hormone (CRH)/brain-derived nerve growth factor (BDNF)/dopamine signaling cascade ([5]). Low-SR fibers are preferentially lost with moderate sound and, with age, a deprivation paradigm that possibly can be centrally compensated (left). In contrast, a critical loss of high-SR fibers might lead to the obstruction of central compensation (right; BK large-conductance, voltage- and Ca2+-activated potassium channel, BLA basolateral complex of the amygdala, HPA hypothalamic-pituitary-adrenal axis, LOC-EF lateral olivocochlear efferent fiber, MR/GR glucocorticoid receptors/mineralocorticoid receptors, TGN trans-Golgi network)
Mentions: Prior to hearing onset, spontaneous Ca2+ APs of IHCs are the result of ATP that is released from the organ of Kölliker and that drives small voltage input in IHCs after birth (Tritsch and Bergles 2010; Tritsch et al. 2007; for a review, see Wang and Bergles 2014). ATP possibly activates IHCs through ligand-gated ionotropic P2X receptors or G-protein-coupled metabotropic P2Y receptors, both of which have been reported to induce increases of the intracellular Ca2+ concentration ([Ca2+]i; Harada 2010). During the period of spontaneous Ca2+ APs, the synaptic machinery of IHCs progressively evolves from multiple spherical bodies, typical of immature hair cells (Fig. 1a), to more confined active zones anchoring a single ribbon (Sobkowicz et al. 1982; Fig. 1b), namely the sub-micrometer electron-dense structures that tether synaptic vesicles (Zenisek et al. 2004). Various excellent reviews have focused on this early developmental period of the inner ear (Castellano-Munoz and Ricci 2014; Fuchs 2005; Marcotti 2012; Moser et al. 2013; Safieddine et al. 2012; Schmitz 2009). The disturbance of ATP signaling during this time has significant adverse effects on the auditory system. This has been shown by reducing ATP-dependent Ca2+ signaling activity in cochlear non-sensory cells, an effect that has been achieved by knocking down the expression of phosphatidylinositol phosphate kinase type 1γ (PIPKIγ), a key enzyme in the generation of phosphatidylinositol 4,5-bisphosphate (Rodriguez et al. 2012). PIPKIγ+/− mice have dramatically elevated hearing thresholds, particularly in response to high-frequency sound. Further studies are essential for an understanding of the profound consequences of this early event in more detail.Fig. 1

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