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Relating structure and function of inner hair cell ribbon synapses.

Wichmann C, Moser T - Cell Tissue Res. (2015)

Bottom Line: Accumulating evidence indicates a highly specialized molecular composition and structure of the presynapse, adapted to suit these high functional demands.Relating structure and function has become an important avenue in addressing these points and has been applied to normal and genetically manipulated hair cell synapses.Here, we review some of the exciting new insights gained from recent studies of the molecular anatomy and physiology of IHC ribbon synapses.

View Article: PubMed Central - PubMed

Affiliation: Molecular Architecture of Synapses Group, Institute for Auditory Neuroscience and InnerEarLab, University Medical Center Göttingen, Göttingen, Germany, cwichma@gwdg.de.

ABSTRACT
In the mammalian cochlea, sound is encoded at synapses between inner hair cells (IHCs) and type I spiral ganglion neurons (SGNs). Each SGN receives input from a single IHC ribbon-type active zone (AZ) and yet SGNs indefatigably spike up to hundreds of Hz to encode acoustic stimuli with submillisecond precision. Accumulating evidence indicates a highly specialized molecular composition and structure of the presynapse, adapted to suit these high functional demands. However, we are only beginning to understand key features such as stimulus-secretion coupling, exocytosis mechanisms, exo-endocytosis coupling, modes of endocytosis and vesicle reformation, as well as replenishment of the readily releasable pool. Relating structure and function has become an important avenue in addressing these points and has been applied to normal and genetically manipulated hair cell synapses. Here, we review some of the exciting new insights gained from recent studies of the molecular anatomy and physiology of IHC ribbon synapses.

No MeSH data available.


Related in: MedlinePlus

Spatial distribution of IHC AZ proteins. a RIBEYE is the main component of the ribbon as shown by pre-embedding immunogold labeling of a P14 IHC synaptic ribbon using an anti-CtBP2 antibody (courtesy of Susann Michanski, InnerEarLab, University Medical Center, Göttingen, Germany); a’ Representative image of an electron micrograph of a round-shaped P9 immature ribbon exhibiting a dotted pattern possibly caused by RIBEYE arrangement (contrast enhanced image in a”), see also schematic representation (a”’). b A P14 mature ribbon with the typical multi-lamellar pattern (contrast enhanced image in b’), see also scheme in b”. Scale bars (a, a”, b’) 100 nm. c A serial 3D reconstruction of a mature ribbon with two distinct morphological vesicle pools (yellow: ribbon-associated vesicles; orange: membrane-proximal vesicles; red: ribbon; blue: AZ membrane; magenta: presynaptic density). c’ The membrane-proximal vesicles (orange) are arranged around the presynaptic density (magenta) that is containing the scaffolding protein bassoon as shown by the pre-embedding immunogold labeling in (d), Scale bar (d) 100 nm (courtesy of Susann Michanski, InnerEarLab, University Medical Center, Göttingen, Germany); d’ 2-color STED image of immunolabeled bassoon (magenta) and CaV1.3 channel clusters (green) in mature IHCs: stripe‐like morphology and closely aligned immunofluorescence of bassoon and CaV1.3 can be observed. Scale image:700 × 700 nm; e, e’ Mathematic model showing the total mean steady state [Ca2+] profile at the AZ membrane (e); e’ effective number of CaV1.3 channels contributing to total mean steady state [Ca2+] as shown in (e). (c, c’, d’, e, e’ modified from Wong et al. 2014, EMBO J; reprinted with permission © 2014 Wong et al.). f Schematic summary of the protein arrangement at mature IHC ribbon synapses
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Fig1: Spatial distribution of IHC AZ proteins. a RIBEYE is the main component of the ribbon as shown by pre-embedding immunogold labeling of a P14 IHC synaptic ribbon using an anti-CtBP2 antibody (courtesy of Susann Michanski, InnerEarLab, University Medical Center, Göttingen, Germany); a’ Representative image of an electron micrograph of a round-shaped P9 immature ribbon exhibiting a dotted pattern possibly caused by RIBEYE arrangement (contrast enhanced image in a”), see also schematic representation (a”’). b A P14 mature ribbon with the typical multi-lamellar pattern (contrast enhanced image in b’), see also scheme in b”. Scale bars (a, a”, b’) 100 nm. c A serial 3D reconstruction of a mature ribbon with two distinct morphological vesicle pools (yellow: ribbon-associated vesicles; orange: membrane-proximal vesicles; red: ribbon; blue: AZ membrane; magenta: presynaptic density). c’ The membrane-proximal vesicles (orange) are arranged around the presynaptic density (magenta) that is containing the scaffolding protein bassoon as shown by the pre-embedding immunogold labeling in (d), Scale bar (d) 100 nm (courtesy of Susann Michanski, InnerEarLab, University Medical Center, Göttingen, Germany); d’ 2-color STED image of immunolabeled bassoon (magenta) and CaV1.3 channel clusters (green) in mature IHCs: stripe‐like morphology and closely aligned immunofluorescence of bassoon and CaV1.3 can be observed. Scale image:700 × 700 nm; e, e’ Mathematic model showing the total mean steady state [Ca2+] profile at the AZ membrane (e); e’ effective number of CaV1.3 channels contributing to total mean steady state [Ca2+] as shown in (e). (c, c’, d’, e, e’ modified from Wong et al. 2014, EMBO J; reprinted with permission © 2014 Wong et al.). f Schematic summary of the protein arrangement at mature IHC ribbon synapses

Mentions: Phylogenetically, ribbons in sensory cells are old structures that occur not only in mammals but also in fishes, amphibians and birds. In the mammalian organ of Corti, they were first described by Smith and Sjöstrand (1961) and are found in both sensory cell types, i.e., IHCs and OHCs (Sobkowicz et al. 1982). The discovery of the protein RIBEYE, initially purified from bovine retina, (Schmitz et al. 2000), as the main and structure-yielding component of ribbons in rat photoreceptors (Schmitz et al. 2000), frog saccular hair cells (Zenisek et al. 2003), zebrafish photoreceptors and bipolar cells (Wan et al. 2005) and mouse cochlear hair cells (Khimich et al. 2005; see also immunogold labeling in Fig. 1a) highlights the conservation of the ribbon in vertebrate evolution (Schmitz 2009). Nonetheless, ribbons still vary greatly in size and shape (Lenzi and von Gersdorff 2001; Moser et al. 2006; Matthews and Fuchs 2010), likely reflecting structural adaptation to the specific needs of the respective synaptic connection for sensory coding.Fig. 1


Relating structure and function of inner hair cell ribbon synapses.

Wichmann C, Moser T - Cell Tissue Res. (2015)

Spatial distribution of IHC AZ proteins. a RIBEYE is the main component of the ribbon as shown by pre-embedding immunogold labeling of a P14 IHC synaptic ribbon using an anti-CtBP2 antibody (courtesy of Susann Michanski, InnerEarLab, University Medical Center, Göttingen, Germany); a’ Representative image of an electron micrograph of a round-shaped P9 immature ribbon exhibiting a dotted pattern possibly caused by RIBEYE arrangement (contrast enhanced image in a”), see also schematic representation (a”’). b A P14 mature ribbon with the typical multi-lamellar pattern (contrast enhanced image in b’), see also scheme in b”. Scale bars (a, a”, b’) 100 nm. c A serial 3D reconstruction of a mature ribbon with two distinct morphological vesicle pools (yellow: ribbon-associated vesicles; orange: membrane-proximal vesicles; red: ribbon; blue: AZ membrane; magenta: presynaptic density). c’ The membrane-proximal vesicles (orange) are arranged around the presynaptic density (magenta) that is containing the scaffolding protein bassoon as shown by the pre-embedding immunogold labeling in (d), Scale bar (d) 100 nm (courtesy of Susann Michanski, InnerEarLab, University Medical Center, Göttingen, Germany); d’ 2-color STED image of immunolabeled bassoon (magenta) and CaV1.3 channel clusters (green) in mature IHCs: stripe‐like morphology and closely aligned immunofluorescence of bassoon and CaV1.3 can be observed. Scale image:700 × 700 nm; e, e’ Mathematic model showing the total mean steady state [Ca2+] profile at the AZ membrane (e); e’ effective number of CaV1.3 channels contributing to total mean steady state [Ca2+] as shown in (e). (c, c’, d’, e, e’ modified from Wong et al. 2014, EMBO J; reprinted with permission © 2014 Wong et al.). f Schematic summary of the protein arrangement at mature IHC ribbon synapses
© Copyright Policy - OpenAccess
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC4487357&req=5

Fig1: Spatial distribution of IHC AZ proteins. a RIBEYE is the main component of the ribbon as shown by pre-embedding immunogold labeling of a P14 IHC synaptic ribbon using an anti-CtBP2 antibody (courtesy of Susann Michanski, InnerEarLab, University Medical Center, Göttingen, Germany); a’ Representative image of an electron micrograph of a round-shaped P9 immature ribbon exhibiting a dotted pattern possibly caused by RIBEYE arrangement (contrast enhanced image in a”), see also schematic representation (a”’). b A P14 mature ribbon with the typical multi-lamellar pattern (contrast enhanced image in b’), see also scheme in b”. Scale bars (a, a”, b’) 100 nm. c A serial 3D reconstruction of a mature ribbon with two distinct morphological vesicle pools (yellow: ribbon-associated vesicles; orange: membrane-proximal vesicles; red: ribbon; blue: AZ membrane; magenta: presynaptic density). c’ The membrane-proximal vesicles (orange) are arranged around the presynaptic density (magenta) that is containing the scaffolding protein bassoon as shown by the pre-embedding immunogold labeling in (d), Scale bar (d) 100 nm (courtesy of Susann Michanski, InnerEarLab, University Medical Center, Göttingen, Germany); d’ 2-color STED image of immunolabeled bassoon (magenta) and CaV1.3 channel clusters (green) in mature IHCs: stripe‐like morphology and closely aligned immunofluorescence of bassoon and CaV1.3 can be observed. Scale image:700 × 700 nm; e, e’ Mathematic model showing the total mean steady state [Ca2+] profile at the AZ membrane (e); e’ effective number of CaV1.3 channels contributing to total mean steady state [Ca2+] as shown in (e). (c, c’, d’, e, e’ modified from Wong et al. 2014, EMBO J; reprinted with permission © 2014 Wong et al.). f Schematic summary of the protein arrangement at mature IHC ribbon synapses
Mentions: Phylogenetically, ribbons in sensory cells are old structures that occur not only in mammals but also in fishes, amphibians and birds. In the mammalian organ of Corti, they were first described by Smith and Sjöstrand (1961) and are found in both sensory cell types, i.e., IHCs and OHCs (Sobkowicz et al. 1982). The discovery of the protein RIBEYE, initially purified from bovine retina, (Schmitz et al. 2000), as the main and structure-yielding component of ribbons in rat photoreceptors (Schmitz et al. 2000), frog saccular hair cells (Zenisek et al. 2003), zebrafish photoreceptors and bipolar cells (Wan et al. 2005) and mouse cochlear hair cells (Khimich et al. 2005; see also immunogold labeling in Fig. 1a) highlights the conservation of the ribbon in vertebrate evolution (Schmitz 2009). Nonetheless, ribbons still vary greatly in size and shape (Lenzi and von Gersdorff 2001; Moser et al. 2006; Matthews and Fuchs 2010), likely reflecting structural adaptation to the specific needs of the respective synaptic connection for sensory coding.Fig. 1

Bottom Line: Accumulating evidence indicates a highly specialized molecular composition and structure of the presynapse, adapted to suit these high functional demands.Relating structure and function has become an important avenue in addressing these points and has been applied to normal and genetically manipulated hair cell synapses.Here, we review some of the exciting new insights gained from recent studies of the molecular anatomy and physiology of IHC ribbon synapses.

View Article: PubMed Central - PubMed

Affiliation: Molecular Architecture of Synapses Group, Institute for Auditory Neuroscience and InnerEarLab, University Medical Center Göttingen, Göttingen, Germany, cwichma@gwdg.de.

ABSTRACT
In the mammalian cochlea, sound is encoded at synapses between inner hair cells (IHCs) and type I spiral ganglion neurons (SGNs). Each SGN receives input from a single IHC ribbon-type active zone (AZ) and yet SGNs indefatigably spike up to hundreds of Hz to encode acoustic stimuli with submillisecond precision. Accumulating evidence indicates a highly specialized molecular composition and structure of the presynapse, adapted to suit these high functional demands. However, we are only beginning to understand key features such as stimulus-secretion coupling, exocytosis mechanisms, exo-endocytosis coupling, modes of endocytosis and vesicle reformation, as well as replenishment of the readily releasable pool. Relating structure and function has become an important avenue in addressing these points and has been applied to normal and genetically manipulated hair cell synapses. Here, we review some of the exciting new insights gained from recent studies of the molecular anatomy and physiology of IHC ribbon synapses.

No MeSH data available.


Related in: MedlinePlus