Short term synaptic plasticity of medial olivocochlear-hair cell synapses is altered by a point mutation in the alpha9alpha10 nAChR

CAROLINA WEDEMEYER; LUCAS VATTINO; JIMENA BALLESTERO; ELEONORA KATZ; ANA BELÉN ELGOYHEN

San Diego, California

Congreso; 39th Midwinter Meeting of the Association for Research in Otolaryngology; 2016

Association for Research in Otolaryngology

Inner hair cells (IHCs) are involved in conveying acoustic information to the central nervous system through the auditory nerve, while OHCs are mainly responsible for the mechanicalamplification of sound. Both hair cells are modulated through medial olivocochlear (MOC) neurons. IHCs receive transient MOC innervation from birth to the onset of hearing in thesecond postnatal week, while MOC fibers synapse with OHCs from the first postnatal week throughout adulthood.The MOC-hair cell synapse is cholinergic, inhibitory, and ismediated by activation of α9α10 nicotinic receptors (nAChRs).We analyzed the properties of synaptic transmission in a knock-in mouse (Kin) bearing a mutation in the α9 nAChR subunit (L9´T) that prolongs cochlear inhibition and enhancesnoise protection (Taranda et. al 2009). Our aim was to determine if there is a consequent change in MOC-hair cell short term plasticity (STP) due to the presence of the L9´T mutation. Synaptic currents (IPSCs) evoked by electrical stimulation of MOC fibers were recorded in IHCs from isolated mouse organ of Corti (apical turn) at postnatal days 9-11. High frequency stimulation, 100 Hz-trains, of MOC fibers caused depression of IPSC amplitudes in IHCs of both wt and Kin mice, (79% and 90% n=4, respectively). Interestingly, a low frequencystimulation of 10 Hz caused depression only in Kin mice (40%, n=5). Release probability analysis suggested that a reduction in the probability of release of synaptic vesicles contributed to depression at 10 Hz (p10/p1=0.77±0.3, n=3). In addition, the amplitude of single successful events decreased towards the end of the train, suggesting that a postsynaptic mechanismalso contributed to synaptic decay (a10/a1=0.64±0.1, n=6). In order to determine the underlying causes for the drop in release probability in 10 Hz-trains we estimated the time course of recovery from synaptic depression. Following a 100 Hz-conditioning train a faster recovery was observed in wt compared to Kin mice (time constant of single-exponential fitwt= 1.21 ± 0.36 s, n=4; Kin: 2.36 ± 0.81 s, n=4.). Results obtained strongly suggest that a change in the kinetic properties of the postsynaptic α9α10 hair cell nAChR is sufficient to alter release efficacy of MOC-IHC synapses. This could result from a homeostatic synaptic change such that presynaptic release probability drops during sustained physiological activity.