Developmental Changes in Synaptic Transmission Properties at the Transient Efferent-Inner Hair Cell Synapse in the Mouse Cochlea.

JAVIER ZORRILLA DE SAN MARTÍN; JIMENA BALLESTERO; PAUL A. FUCHS; ANA BELÉN ELGOYHEN; ELEONORA KATZ

Baltimore

Congreso; Thirty-fourth annual midwinter research meeting of the association for research in otolaryngology; 2011

Association for Research in Otolaryngology

From birth until the onset of hearing (postnatal day (P) 12), IHCs are transiently innervated by cholinergic medial olivocochlear (MOC) fibers. At this synapse, transmitter release is supported by both N- and P/Q-type voltage gatedcalcium channels (VGCCs) (Zorrilla de San Martín et al., J. Neurosci 2010). The fast formation and retraction of the MOC-IHC synapse suggest there may also beassociated changes in synaptic transmission throughout this period. Short term plasticity (STP) is a dynamic process that depends on the balance between facilitation and depression of synaptic responses caused by preceding activity. Our goal is to determine whether there are changes in STP at the MOC-IHC synapse during development and, if so, to understand the mechanisms underlying them. Synaptic activity was recorded in voltage clamped IHCs from excised apical turns of the mouse cochlea at two developmental stages (P5-7 and P9-11) during electrical stimulation of the MOC fibers. Ten-pulse trains at 10, 20, 40 and 100 Hz applied to P5-7 MOC-IHC synapses led to 1.8±0.3; 1.7±0.2; 1.8±0.3 and 2±0.4-fold increase in synaptic efficacy, respectively, estimated as the ratio between the mean amplitude of the fifth and the first evoked synaptic current (S5/S1); n=7-10. The same protocols applied to P9-11 synapses led to a progressivedecrease of the S5/S1 value (0.8±0.1; 0.7±0.1; 0.6±0.1; 0.4±0.1 for the 10, 20, 40 and 100 Hz trains, respectively; n=12-18). Depression upon high frequency stimulation at P9-11 was reversed to facilitation when reducing quantal output either by decreasing [Ca2+]o or by blocking P/Qtype VGCCs with ω-Agatoxin IVA (200 nM). Our results show there is a developmental switch from facilitation todepression upon high frequency stimulation consistent with the increment in the probability of release. We are now studying whether these changes in synaptic transmission can be accounted for by differences in the coupling between calcium influx and transmitter release.