Short-term synaptic plasticity determines the level of olivocochlear inhibition to mammalian auditory hair cells

BALLESTERO J; ZORRILA DE SAN MARTIN J; GOUTMAN J; FUCHS PA; ELGOYHEN AB; KATZ, E

Lisboa

Workshop; 48th Inner Ear Biology Workshop; 2011

In mammals, the gain control of auditory inputs is exerted by medial olivocochlear (MOC) neurons that innervate cochlear outer hair cells (OHCs). OHCs mechanically amplify the incoming sound waves by virtue of their electromotile properties while the MOC system reduces the gain of auditory inputs by inhibiting OHCs function. How this process is orchestrated at the synaptic level remains unknown. In this study, MOC firing was evoked by electrical stimulation while OHCs postsynaptic responses were monitored by whole-cell recordings in excised mouse organs of Corti.  We confirmed, by pharmacological methods, that electrically evoked inhibitory postsynaptic currents (eIPSCs) are mediated by alpha9alpha10 nAChRs functionally coupled to calcium-activated SK2 channels. Synaptic release occurred with low probability (Psuccess = 0.25±0.06) when MOC fibers were stimulated at 1Hz. However, upon raising the stimulation frequency, the reliability of release increased due to presynaptic facilitation. Also, the relatively slow decay of eIPSCs gave rise to temporal summation at stimulation frequencies above 10 Hz. This indicates that short-term plasticity (STP) at this synapse has both presynaptic and postsynaptic determinants. The combined effect of facilitation and summation resulted in a frequency-dependent increase in the average amplitude of eIPSCs (Response increments were 4.2±0.3; 7.5±0.8, 12.4±0.7, 21.6±5.9 for 25, 50, 60 and 80 Hz, respectively). Thus, the STP properties of the MOC-OHC synapse determine the level of OHC?s inhibition. In preliminary experiments in IHCs from knock-in mice expressing a slow-desensitizing alpha9alpha10 nAChR, synaptic responses to MOC high frequency activity present slower rise times and reduced depression than their wild-type littermates. Interestingly, these changes in synaptic responses closely resemble the alterations in the time course of MOC inhibition measured in-vivo in the same animal model (Taranda et al., 2009). We therefore postulate that olivocohlear inhibition of auditory function is finely tuned by the dynamics of the MOC-OHC synapse.