Short-Term Synaptic Plasticity at the Medial Olivocochlear Hair Cell Synapse in α9L9’T Knock-In Mice

BALLESTERO J; ALVAREZ HEDU¡§¢N F; FUCHS PA; KATZ E; ELGOYHEN AB

San Diego

Congreso; 35th Midwinter Meeting of the Association for Research in Otolaryngology; 2012

Association for Research in Otolaryngology

Cochlear amplification is regulated by the central nervous system through medial olivocochlear (MOC) neurons that project from the brainstem and synapse onto outer hair cells (OHCs). The OHCs inhibitory postsynaptic currents (IPSCs) in the OHCs are mediated by the activation of α9α10 nicotinic receptors (nAChRs) and SK2 calcium-activated potassium channels. We have generated a mouse with a point mutation (L9’T) in the α9α10 nAChR that produces longer-lasting inhibitory postsynaptic currents and changes the magnitude and the dynamics of the efferent-mediated inhibition of cochlear responses (Taranda et al. Plos Biology, 2009). Our goal is now to determine if there is a consequent change in the short-term plasticity (STP) properties of the MOC-hair cell synapse. In order to do so we used the transient MOC-inner hair cells (IHCs) synapse as a model. Synaptic activity was recorded in voltage-clamped IHCs from excised apical turns of wild-type (wt) or α9L9’T knock-in (kin) mouse cochlea (9-11 postnatal days) during electrical stimulation of the MOC fibers. As was previously shown for spontaneous IPSCs, electrically evoked IPSCs in kin mice presented longer decay times (τdecay wt: 46 ± 3 ms; kin: 267 ± 35 ms) and smaller peak amplitudes (Ipeak wt: -39 ± 8 pA; kin: -20 ± 3 pA) compared to those of wt IHCs. The mean quantum content of the MOC-IHC synapse showed no significant differences between wt (1.0 ± 0.3) and kin (0.7 ± 0.2) mice, indicating no alterations in basal synaptic efficacy. In wt IHCs, prolonged high frequency stimulation produced an increase in the postsynaptic response during the 1st second, followed by depression that produced ~80% decay in the response. In kin mice, peak responses were reached after ~3 sec of stimulation and then decayed to ~50%. These results show that changes in the dynamics of the nAChR induce dramatic changes in the MOC-hair cell synapse STP properties.