Abstract
The organ of Corti, the auditory mammalian sensory epithelium, contains two types of mechanotransducer cells, inner hair cells (IHCs) and outer hair cells (OHCs). IHCs are involved in conveying acoustic stimuli to the CNS, while OHCs are implicated in the fine tuning and amplification of sounds. OHCs are innervated by medial olivocochlear (MOC) cholinergic efferent fibers. The functional characteristics of the MOC-OHC synapse during maturation were assessed by electrophysiological and pharmacological methods in mouse organs of Corti at postnatal day 11 (P11)-P13, hearing onset in altricial rodents, and at P20-P22 when the OHCs are morphologically and functionally mature. Synaptic currents were recorded in whole-cell voltage-clamped OHCs while electrically stimulating the MOC fibers. A progressive increase in the number of functional MOC-OHC synapses, as well as in their strength and efficacy, was observed between P11-13 and P20-22. At hearing onset, the MOC-OHC synapse presented facilitation during MOC fibers high-frequency stimulation that disappeared at mature stages. In addition, important changes were found in the VGCC that are coupled to transmitter release. Ca2+ flowing in through L-type VGCCs contribute to trigger ACh release together with P/Q- and R-type VGCCs at P11-P13, but not at P20-P22. Interestingly, N-type VGCCs were found to be involved in this process at P20-P22, but not at hearing onset. Moreover, the degree of compartmentalization of calcium channels with respect to BK channels and presynaptic release components significantly increased from P11-P13 to P20-P22. These results suggest that the MOC-OHC synapse is immature at the onset of hearing.SIGNIFICANCE STATEMENT The functional expression of both VGCCs and BK channels, as well as their localization with respect to the presynaptic components involved in transmitter release, are key elements in determining synaptic efficacy. In this work, we show dynamic changes in the expression of VGCCs and Ca2+-dependent BK K+ channels coupled to ACh release at the MOC-OHC synapse and their shift in compartmentalization during postnatal maturation. These processes most likely set the short-term plasticity pattern and reliability of the MOC-OHC synapse on high-frequency activity.
Highlights
The organ of Corti, the sensory epithelium of the mammalian inner ear, contains two types of mechanoreceptor cells, inner hair cells (IHCs) and outer hair cells (OHCs), that transform sounds into electrical signals
The present results show that the facilitation of responses on high-frequency stimulation is lost as the MOC–OHC synapse matures and transmitter release becomes more reliable on lowfrequency firing of the MOC fibers
Bearing in mind that BK channels have been shown to be significantly relevant in controlling action potential firing at high frequencies (Gu et al, 2007) and considering that in vivo MOC fibers fire at frequencies ranging from 1 to 120 Hz (Robertson and Gummer, 1985; Liberman and Brown, 1986; Atluri and Regehr, 1996; Müller et al, 2010), we investigated whether BK channels are involved in signaling at the MOC–OHC synapse during high-frequency activity of the MOC fibers
Summary
The organ of Corti, the sensory epithelium of the mammalian inner ear, contains two types of mechanoreceptor cells, inner hair cells (IHCs) and outer hair cells (OHCs), that transform sounds into electrical signals. IHCs release glutamate and activate the auditory nerve fibers contacting them (Hudspeth, 1997; Fuchs et al, 2003), while OHCs change their length in response to sound-driven voltage variations (Brownell et al, 1985). These shape changes in the OHCs, termed electromotility, are powered by the motor protein prestin and are part of the mechanical feedback process that amplifies low-level sounds (Dallos, 2008). We have recently shown that the dynamics of the MOC–OHC synapse directly determine the efficacy of the MOC feedback to the cochlea, being a main player in the gain control of the auditory periphery (Ballestero et al, 2011; Wedemeyer et al, 2018)
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