Structure and function of the hair cell ribbon synapse

Abstract

Faithful information transfer at the hair cell afferent synapse requires synaptic transmission to be both reliable and temporally precise. The release of neurotransmitter must exhibit both rapid on and off kinetics to accurately follow acoustic stimuli with a periodicity of 1 ms or less. To ensure such remarkable temporal fidelity, the cochlear hair cell afferent synapse undoubtedly relies on unique cellular and molecular specializations. While the electron microscopy hallmark of the hair cell afferent synapse--the electron-dense synaptic ribbon or synaptic body--has been recognized for decades, dissection of the synapse's molecular make-up has only just begun. Recent cell physiology studies have added important insights into the synaptic mechanisms underlying fidelity and reliability of sound coding. The presence of the synaptic ribbon links afferent synapses of cochlear and vestibular hair cells to photoreceptors and bipolar neurons of the retina. This review focuses on major advances in understanding the hair cell afferent synapse molecular anatomy and function that have been achieved during the past years.

Figure 1

Hair cell ribbon synapse. Electron micrograph of an inner hair cell afferent synapse of an 8-week-old mouse. The ribbon (rib) is anchored to the presynaptic plasma membrane and faces the postsynaptic density (PSD) of the auditory nerve fibers. The arrowhead and the star indicate a ribbon-associated synaptic vesicle and a free cytoplasmic coated vesicle, respectively.

Figure 2

Molecular composition of the hair cell synapse. (A) Montage of a Nomarski image (note the hair cell bundles) and a confocal reconstruction of the mouse organ of Corti with immunolabeled ribbons (stained for RIBEYE/CtBP2, red) and postsynaptic transmitter receptor clusters (GluR2/3 glutamate receptor subtypes, green). Presumptive hair cell border (white) and postsynaptic fibers (orange) contacting an IHC were drawn illustration. (B) Previously identified molecular determinants of the hair cell ribbon synapse. ¹Safieddine & Wenthold, 1999; ²Furness & Lawton, 2003; ³Eybalin et al., 2002; ⁴Schmitz et al., 2006; ⁵Khimich et al., 2005; ⁶Platzer et al., 2000; ⁷Brandt, Striessnig & Moser, 2003; ⁸Brandt, Khimich & Moser, 2005; ⁹Matsubara et al., 1996; ¹⁰Eybalin et al., 2004.

Figure 3

Morphology of synaptic ribbons. (a, b and c) Electron micrographs of inner hair cell ribbon synapses of 8-week-old mouse. Ribbons are attached to the plasma membrane and surrounded by a monolayer of synaptic vesicles. Colored dots in (b) illustrate the morphologically defined classes of synaptic vesicles: red dots indicate the docked vesicle associated with the ribbon; yellow marks ribbon- associated SV which are not docked and green indicates outlying cytoplasmic vesicles. (d) Slice through an osmium-stained frog saccular hair cell synapse, reconstructed by electron tomography. Note the round shape of the synaptic body in contrast to the elipsoid one of the mouse. (e) Three-dimensional structure of presynaptic organelles from the same reconstruction shown in (d). The synaptic body (blue) is open and lies adjacent to the hair cell’s plasma membrane in red. Synaptic body-associated vesicles (yellow) surround the SB; outlying vesicles (green) lie further out in the cytoplasm. Also visible are coated vesicles (gold) and cisterns (purple).