Compound synapses within the GABAergic innervation of the auditory inner hair cells in the adolescent mouse

Abstract

Ultrastructural investigation of the gamma-aminobutyric acid (GABA) component of the inner spiral bundle in adolescent mice revealed a pathway of glutamic acid decarboxylase (GAD)-positive and -negative fibers and vesiculated endings that contact inner hair cells and their afferents through a complex of axosomatic and axodendritic synapses. Ultrastructural details were investigated by using conventional electron microscopy. Several synaptic arrangements were observed: Main axosomatic synapses form between vesiculated endings and individual or adjoining inner hair cells (interreceptor synapses). Spinous synapses form on long, spinelike processes that protrude from inner hair cells to reach distant efferent endings. The efferent endings associate with inner hair cells and their synaptic afferents through compound synapses-serial, "converging," and triadic-otherwise characteristic of sensory relay nuclei. Serial synapses form by the sequential presynaptic alignment of the efferent-->receptor-->afferent components. Converging synapses result from the simultaneous apposition of a receptor ribbon synapse and a presynaptic efferent terminal on a recipient afferent dendrite. Triadic synapses comprise a vesiculated efferent ending in contact with an inner hair cell and with its synaptic afferent. Additionally, efferent endings may form simple axodendritic and axoaxonal synapses with GAD-negative vesiculated endings. The combination of different synaptic arrangements leads to short chains of compound synapses. It is assumed that these synaptic patterns seen in the adolescent mouse represent adult synaptology. The patterns of synaptic connectivity suggest an integrative role for the GABA/GAD lateral efferent system, and imply its involvement in the pre- and postsynaptic modulation of auditory signals.

Efferent synapses return to inner hair cells in the aging cochlea

“…Sobkowicz and colleagues (1994; 1997; 2002) also identified axosomatic efferent terminals in the cochlear apex and mid-turn of developing mice of the outbred ICR strain. As in aging C57 mice, efferents in young ICR mice occasionally formed synapses with two IHCs, termed “inter-receptor synapses.” GABAergic signaling is known to produce neurotrophic effects (Lauder, 1993) and has been suggested to play a role in the maintenance of hair cells and auditory nerve fibers (Maison et al, 2006; Ruel et al, 2001).…”

Potential of embryonic stem cell‐derived neurons for synapse formation with auditory hair cells

“…8D) showing the existence of synaptic contacts. However, synapse ribbons, which are included in characteristics for afferent synaptic contacts between IHCs and SGN dendrites (Sobkowicz, 1992; Sobkowicz et al, 1997), were not observed in the base of IHCs attaching to ESC‐derived nerve endings.…”

“…This represents the first evidence of synapse formation between ESC‐derived neurons and IHCs. In normal cochleae of mature mice, afferent synapse contacts at the base of IHCs are characterized by the presence of synaptic ribbons and by a postsynaptic membrane density on the dendrite (Sobkowicz, 1992; Sobkowicz et al, 1997). However, in TEM analysis, no synaptic ribbons were found in the base of IHCs adjacent to ESC‐derived nerve endings.…”

“…The aim of the present study was therefore to determine the synapse formation ability of ESC‐derived neurons with auditory HCs. In the cochlea, there are the afferent synapses between the peripheral fibers of spiral ganglion neurons and sensory HCs (Sobkowicz, 1992) and the efferent synapses, both axosomatic with the sensory HCs and axodendritic with the peripheral afferents (Sobkowicz et al, 1997, 2002). We cocultured mouse ESC‐derived neural progenitors with explants of mouse auditory sensory epithelia and morphologically examined the neural connections that arose between ESC‐derived neurons and HCs.…”

Disruption of lateral olivocochlear neurons with a dopaminergic neurotoxin depresses spontaneous auditory nerve activity

“…LOC innervation is biased towards the IHC modiolar side; there, low-SR fibers are innervated by twice as many LOC terminals as high-SR fibers [22]. In addition, a small number of LOC neurons synapse directly on IHCs [21, 40, 41]. LOC efferents contain a variety of neurotransmitters, including dopamine (DA), dynorphin (dyn), enkepalin (enk), γ-aminobutyric acid (GABA), acetylcholine (ACh), and calcitonin-gene-related peptide (CGRP) [for reviews, see 1, 7, 12, 16, 18, 34].…”