Limits...
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

Principle of functional heterogeneity in IHCs. a Schematic of an organ of Corti showing afferent and efferent innervations at IHCs. Modified from Meyer and Moser 2010, Curr Opin Otolaryngol Head Neck Surg, reprinted with permission from © 2010 Wolters Kluwer Health. b, b’ Heterogeneous Ca2+ signaling in IHCs. b Mean and SD of ΔF (gray) as a function of depolarizing potential (Vm), obtained from spot-detection experiments at the center of the Ca2+ microdomain; ΔF was averaged over the last 15 ms of a 20-ms stimulus. ΔF (mean gray) and ICa (mean black) show a similar voltage dependence (thin lines corresponding SDs). b’ Heterogeneous voltage dependence and Ca2+ channel number of synaptic Ca2+ channel clusters in IHCs. Pronounced variability in the voltage dependence of activation, even within the same cell (dashed traces individual data curves from 3 Ca2+ microdomains in an IHC). Modified from Frank et al. (2009), PNAS USA, with permission from © Frank et al. c, c’ Colorized spatial distribution of vesicles and cisterns around the ribbon in low- and high-spontaneous rate (SR) fibers. Sections through a high-SR (c) and a low-SR (c’) synapse containing the synaptic ribbon are shown with cisternal (maroon) and vesicular (green) profiles. Scale bar (cm c’) 200 nm. d, d’ Distribution of docked vesicles and cisterns. d Mean density (± SE) of docked vesicles, i.e., within 20 nm of the presynaptic density along the presynaptic membrane. d’ Mean number (± SE) of cisterns within 20 nm of the presynaptic density versus distance along the presynaptic membrane is shown for all synapses. In addition, counts for low- and high-SR synapses are plotted separately. Rectangle the area of significant differences between low- and high-SR synapses. SE standard error; SR spontaneous rate. (c, c’, d, d’ modified from Kantardzhieva et al. 2013, J Comp Neurol, reprinted with permission from © 2013 Wiley Periodicals)
© Copyright Policy - OpenAccess
Related In: Results  -  Collection


getmorefigures.php?uid=PMC4487357&req=5

Fig2: Principle of functional heterogeneity in IHCs. a Schematic of an organ of Corti showing afferent and efferent innervations at IHCs. Modified from Meyer and Moser 2010, Curr Opin Otolaryngol Head Neck Surg, reprinted with permission from © 2010 Wolters Kluwer Health. b, b’ Heterogeneous Ca2+ signaling in IHCs. b Mean and SD of ΔF (gray) as a function of depolarizing potential (Vm), obtained from spot-detection experiments at the center of the Ca2+ microdomain; ΔF was averaged over the last 15 ms of a 20-ms stimulus. ΔF (mean gray) and ICa (mean black) show a similar voltage dependence (thin lines corresponding SDs). b’ Heterogeneous voltage dependence and Ca2+ channel number of synaptic Ca2+ channel clusters in IHCs. Pronounced variability in the voltage dependence of activation, even within the same cell (dashed traces individual data curves from 3 Ca2+ microdomains in an IHC). Modified from Frank et al. (2009), PNAS USA, with permission from © Frank et al. c, c’ Colorized spatial distribution of vesicles and cisterns around the ribbon in low- and high-spontaneous rate (SR) fibers. Sections through a high-SR (c) and a low-SR (c’) synapse containing the synaptic ribbon are shown with cisternal (maroon) and vesicular (green) profiles. Scale bar (cm c’) 200 nm. d, d’ Distribution of docked vesicles and cisterns. d Mean density (± SE) of docked vesicles, i.e., within 20 nm of the presynaptic density along the presynaptic membrane. d’ Mean number (± SE) of cisterns within 20 nm of the presynaptic density versus distance along the presynaptic membrane is shown for all synapses. In addition, counts for low- and high-SR synapses are plotted separately. Rectangle the area of significant differences between low- and high-SR synapses. SE standard error; SR spontaneous rate. (c, c’, d, d’ modified from Kantardzhieva et al. 2013, J Comp Neurol, reprinted with permission from © 2013 Wiley Periodicals)

Mentions: Interestingly, the size and shape of ribbons appear to be highly variable and dynamic. In fact, in photoreceptors, these parameters strongly correlate with activity in light (silent) or dark (active) conditions (Spiwoks-Becker et al. 2013). Similarly, in IHCs, a diverse spectrum of ribbons has also been observed (Bodian 1978; Sobkowicz et al. 1982; Merchan-Perez and Liberman 1996; Wong et al. 2014). The specific ultrastructural properties seem to depend on several factors: (1) the maturation/age (see section above), (2) position within the inner hair cell and maybe also (3) dynamic adaptation to activity. A pioneering study in cats was one of the first to identify the correlation between structural heterogeneity of ribbon synapses and functional characteristics of auditory nerve fibers (Merchan-Perez and Liberman 1996). Surprisingly, large AZs with big and/or several ribbons, supposedly reflecting large presynaptic strength, seem to drive SGNs with low spontaneous rate and high thresholds (see also scheme in Fig. 2a). Whereas this conundrum remains unsolved, the mechanisms of functional presynaptic heterogeneity are now beginning to be understood. Evidence for such heterogeneity within individual IHCs was obtained using confocal imaging of presynaptic Ca2+ influx (Frank et al. 2009; see also Fig. 2b, b’). This study showed that presynaptic Ca2+ signals varied substantially in amplitude and voltage-dependence among the AZs within individual IHCs. The amplitude of the Ca2+ signal scaled with ribbon size as approximated by simultaneous imaging of a fluorescently tagged RIBEYE-binding peptide (Frank et al. 2009) and seemed to be greater at the neural side of the IHCs (Meyer et al. 2009). Linking such estimates to the functional and morphological properties of the postsynaptic neurons will be an important task for future studies. So far, correlative arguments based on coincidental changes in maximal strength of presynaptic Ca2+ influx and postsynaptic spiking during development and upon genetic disruption as well as modeling have been brought forward to argue that strong synapses drive SGNs that have high spontaneous rates and low thresholds (Wong et al. 2013). Interestingly, an inverse correlation of pre- and postsynaptic parameters of synaptic strength has recently been reported for mouse IHCs: Liberman et al. (2011) suggested that synapses with many AMPA receptors exhibit small ribbons. The authors favored the interpretation that the SGNs inserting at the neural (modiolar) face of IHCs exhibit low spontaneous rates and high thresholds despite their corresponding large IHC AZs, because they have a smaller complement of AMPA receptors than those at the neural (pillar) side. This would agree with the conclusion of the classical study, which showed a neural–abneural gradient of AZ size using electron microscopy for cat IHCs whereby large AZs faced SGNs with low spontaneous rates and high thresholds (Merchan-Perez and Liberman 1996). In a laborious approach, the authors traced 11 functionally-characterized fibers to the IHCs using serial 3D reconstructions of ultrathin sections. In this way, it was possible to directly correlate morphological parameters such as ribbon length, fiber contact area, synaptic plaque area and synaptic vesicle numbers to the functional parameters determined prior to fiber labeling using single unit recordings. Recently, such a gradient was also suggested for mouse IHCs and reported to be influenced by the lateral olivocochlear innervation (Yin et al. 2014). The segregation of nerve fibers on neural and abneural sides was further observed in a study investigating the abundance of mitochondria in postsynaptic terminals. Here, postsynaptic boutons facing the abneural side seem to harbor more mitochondria (Francis et al. 2004). Monitoring EPSCs from single afferent boutons, which is a suitable method to address synaptic function on the level of individual release sites (Glowatzki and Fuchs 2002), further showed differences among synapses. In these experiments, varying fractions of multiphasic EPSCs were observed and proposed to underlie the diverse firing properties of SGNs (Grant et al. 2010).Fig. 2


Relating structure and function of inner hair cell ribbon synapses.

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

Principle of functional heterogeneity in IHCs. a Schematic of an organ of Corti showing afferent and efferent innervations at IHCs. Modified from Meyer and Moser 2010, Curr Opin Otolaryngol Head Neck Surg, reprinted with permission from © 2010 Wolters Kluwer Health. b, b’ Heterogeneous Ca2+ signaling in IHCs. b Mean and SD of ΔF (gray) as a function of depolarizing potential (Vm), obtained from spot-detection experiments at the center of the Ca2+ microdomain; ΔF was averaged over the last 15 ms of a 20-ms stimulus. ΔF (mean gray) and ICa (mean black) show a similar voltage dependence (thin lines corresponding SDs). b’ Heterogeneous voltage dependence and Ca2+ channel number of synaptic Ca2+ channel clusters in IHCs. Pronounced variability in the voltage dependence of activation, even within the same cell (dashed traces individual data curves from 3 Ca2+ microdomains in an IHC). Modified from Frank et al. (2009), PNAS USA, with permission from © Frank et al. c, c’ Colorized spatial distribution of vesicles and cisterns around the ribbon in low- and high-spontaneous rate (SR) fibers. Sections through a high-SR (c) and a low-SR (c’) synapse containing the synaptic ribbon are shown with cisternal (maroon) and vesicular (green) profiles. Scale bar (cm c’) 200 nm. d, d’ Distribution of docked vesicles and cisterns. d Mean density (± SE) of docked vesicles, i.e., within 20 nm of the presynaptic density along the presynaptic membrane. d’ Mean number (± SE) of cisterns within 20 nm of the presynaptic density versus distance along the presynaptic membrane is shown for all synapses. In addition, counts for low- and high-SR synapses are plotted separately. Rectangle the area of significant differences between low- and high-SR synapses. SE standard error; SR spontaneous rate. (c, c’, d, d’ modified from Kantardzhieva et al. 2013, J Comp Neurol, reprinted with permission from © 2013 Wiley Periodicals)
© Copyright Policy - OpenAccess
Related In: Results  -  Collection

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

Fig2: Principle of functional heterogeneity in IHCs. a Schematic of an organ of Corti showing afferent and efferent innervations at IHCs. Modified from Meyer and Moser 2010, Curr Opin Otolaryngol Head Neck Surg, reprinted with permission from © 2010 Wolters Kluwer Health. b, b’ Heterogeneous Ca2+ signaling in IHCs. b Mean and SD of ΔF (gray) as a function of depolarizing potential (Vm), obtained from spot-detection experiments at the center of the Ca2+ microdomain; ΔF was averaged over the last 15 ms of a 20-ms stimulus. ΔF (mean gray) and ICa (mean black) show a similar voltage dependence (thin lines corresponding SDs). b’ Heterogeneous voltage dependence and Ca2+ channel number of synaptic Ca2+ channel clusters in IHCs. Pronounced variability in the voltage dependence of activation, even within the same cell (dashed traces individual data curves from 3 Ca2+ microdomains in an IHC). Modified from Frank et al. (2009), PNAS USA, with permission from © Frank et al. c, c’ Colorized spatial distribution of vesicles and cisterns around the ribbon in low- and high-spontaneous rate (SR) fibers. Sections through a high-SR (c) and a low-SR (c’) synapse containing the synaptic ribbon are shown with cisternal (maroon) and vesicular (green) profiles. Scale bar (cm c’) 200 nm. d, d’ Distribution of docked vesicles and cisterns. d Mean density (± SE) of docked vesicles, i.e., within 20 nm of the presynaptic density along the presynaptic membrane. d’ Mean number (± SE) of cisterns within 20 nm of the presynaptic density versus distance along the presynaptic membrane is shown for all synapses. In addition, counts for low- and high-SR synapses are plotted separately. Rectangle the area of significant differences between low- and high-SR synapses. SE standard error; SR spontaneous rate. (c, c’, d, d’ modified from Kantardzhieva et al. 2013, J Comp Neurol, reprinted with permission from © 2013 Wiley Periodicals)
Mentions: Interestingly, the size and shape of ribbons appear to be highly variable and dynamic. In fact, in photoreceptors, these parameters strongly correlate with activity in light (silent) or dark (active) conditions (Spiwoks-Becker et al. 2013). Similarly, in IHCs, a diverse spectrum of ribbons has also been observed (Bodian 1978; Sobkowicz et al. 1982; Merchan-Perez and Liberman 1996; Wong et al. 2014). The specific ultrastructural properties seem to depend on several factors: (1) the maturation/age (see section above), (2) position within the inner hair cell and maybe also (3) dynamic adaptation to activity. A pioneering study in cats was one of the first to identify the correlation between structural heterogeneity of ribbon synapses and functional characteristics of auditory nerve fibers (Merchan-Perez and Liberman 1996). Surprisingly, large AZs with big and/or several ribbons, supposedly reflecting large presynaptic strength, seem to drive SGNs with low spontaneous rate and high thresholds (see also scheme in Fig. 2a). Whereas this conundrum remains unsolved, the mechanisms of functional presynaptic heterogeneity are now beginning to be understood. Evidence for such heterogeneity within individual IHCs was obtained using confocal imaging of presynaptic Ca2+ influx (Frank et al. 2009; see also Fig. 2b, b’). This study showed that presynaptic Ca2+ signals varied substantially in amplitude and voltage-dependence among the AZs within individual IHCs. The amplitude of the Ca2+ signal scaled with ribbon size as approximated by simultaneous imaging of a fluorescently tagged RIBEYE-binding peptide (Frank et al. 2009) and seemed to be greater at the neural side of the IHCs (Meyer et al. 2009). Linking such estimates to the functional and morphological properties of the postsynaptic neurons will be an important task for future studies. So far, correlative arguments based on coincidental changes in maximal strength of presynaptic Ca2+ influx and postsynaptic spiking during development and upon genetic disruption as well as modeling have been brought forward to argue that strong synapses drive SGNs that have high spontaneous rates and low thresholds (Wong et al. 2013). Interestingly, an inverse correlation of pre- and postsynaptic parameters of synaptic strength has recently been reported for mouse IHCs: Liberman et al. (2011) suggested that synapses with many AMPA receptors exhibit small ribbons. The authors favored the interpretation that the SGNs inserting at the neural (modiolar) face of IHCs exhibit low spontaneous rates and high thresholds despite their corresponding large IHC AZs, because they have a smaller complement of AMPA receptors than those at the neural (pillar) side. This would agree with the conclusion of the classical study, which showed a neural–abneural gradient of AZ size using electron microscopy for cat IHCs whereby large AZs faced SGNs with low spontaneous rates and high thresholds (Merchan-Perez and Liberman 1996). In a laborious approach, the authors traced 11 functionally-characterized fibers to the IHCs using serial 3D reconstructions of ultrathin sections. In this way, it was possible to directly correlate morphological parameters such as ribbon length, fiber contact area, synaptic plaque area and synaptic vesicle numbers to the functional parameters determined prior to fiber labeling using single unit recordings. Recently, such a gradient was also suggested for mouse IHCs and reported to be influenced by the lateral olivocochlear innervation (Yin et al. 2014). The segregation of nerve fibers on neural and abneural sides was further observed in a study investigating the abundance of mitochondria in postsynaptic terminals. Here, postsynaptic boutons facing the abneural side seem to harbor more mitochondria (Francis et al. 2004). Monitoring EPSCs from single afferent boutons, which is a suitable method to address synaptic function on the level of individual release sites (Glowatzki and Fuchs 2002), further showed differences among synapses. In these experiments, varying fractions of multiphasic EPSCs were observed and proposed to underlie the diverse firing properties of SGNs (Grant et al. 2010).Fig. 2

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