Developmental changes in short term plasticity properties at the transient medial olivocochlear-inner hair cell (MOC-IHC) synapse.

JAVIER ZORRILLA DE SAN MARTÍN; JIMENA BALLESTERO; ANA BELÉN ELGOYHEN; ELEONORA KATZ

Lisboa

Workshop; Inner Ear Biology Workshop; 2011

From birth until the onset of hearing (postnatal day (P)12), IHCs are transiently innervated by cholinergic medial olivocochlear (MOC) fibers. Evoked transmitter release at P9-11 has a quantal content (m) of 2, is supported by N- and P/Q-type voltage-gated calcium channels (VGCCs) and negatively modulated by BK-type K+ channels (Zorrilla de San Martín et al., J. Neurosci 2010). The fast formation and retraction of the MOC-IHC synapse suggests there may be associated changes in synaptic transmission. Short term plasticity (STP) is a dynamic process that depends on the balance between facilitation and depression of synaptic responses caused by preceding activity. To determine whether there are changes in the STP properties at the MOC-IHC synapse during development synaptic activity was recorded in voltage-clamped IHCs from excised apical turns of the mouse cochlea during electrical stimulation of the MOC fibers at two postnatal ages (P5-7 and P9-11). In P5-7 mice, omega-AgatoxinIVA (200 nM), a P/Q-type VGCC antagonist, reduced m to 37±6% while iberiotoxin (100 nM), a BK antagonist, increased this parameter to 193±11% (control=0.75±0.33). Therefore, transmitter release is also partially supported by P/Q-type VGCCs and negatively modulated by BK channels at this stage. Ten-pulse trains at 40 and 100 Hz applied at P5-7 synapses caused a 1.8±0.3 and 2±0.4-fold increase in synaptic efficacy, respectively. At P9-11, this caused a progressive decrease in synaptic efficacy (0.6±0.1; 0.4±0.1 for the 40 and 100 Hz trains, respectively). Depression upon high frequency stimulation at P9-11 was reversed to facilitation when reducing m by decreasing [Ca2+]o or by blocking P/Q-type VGCCs and intensified by blocking BK channels. Moreover, facilitation at P5-7 was prevented by increasing [Ca2+]o or by blocking BK channels. Our results show there is a developmental switch from facilitation to depression upon high frequency stimulation consistent with the increment in the efficacy of the synapse.