Developmental synaptic changes at the transient olivocochlear-inner hair cell synapse

KEARNEY, GRACIELA; ELGOYHEN, ANA BELÉN; KEARNEY, GRACIELA; ELGOYHEN, ANA BELÉN; ZORRILLA DE SAN MARTÍN, JAVIER; VATTINO, LUCAS G.; WEDEMEYER, CAROLINA; KATZ, ELEONORA; ZORRILLA DE SAN MARTÍN, JAVIER; VATTINO, LUCAS G.; WEDEMEYER, CAROLINA; KATZ, ELEONORA

JOURNAL OF NEUROSCIENCE

SOC NEUROSCIENCE

Año: 2019 vol. 39 p. 3360 - 3375

0270-6474

In the mature mammalian cochlea, inner hair cells (IHCs) are mainly innervated by afferent fibers that convey sound information to the CNS. During postnatal development, however, medial olivocochlear (MOC) efferent fibers transiently innervate the IHCs. The MOC-IHC synapse, functional from postnatal day 0 (P0) to hearing onset (P12), undergoes dramatic changes in the sensitivity to acetylcholine (ACh) and in the expression of key postsynaptic proteins. To evaluate whether there are associated changes in the properties of ACh release during this period, we used a cochlear preparation from mice of either sex at P4, P6-P7, and P9-P11 and monitored transmitter release from MOC terminals in voltage-clamped IHCs in the whole-cell configuration. The quantum content increased 5.6× from P4 to P9-P11 due to increases in the size and replenishment rate of the readily releasable pool of synaptic vesicles without changes in their probability of release or quantum size. This strengthening in transmission was accompanied by changes in short-term plasticity properties, which switched from facilitation at P4 to depression at P9-P11. We have previously shown that at P9-P11, ACh release is supported by P/Q- and N-type voltage-gated calcium channels (VGCCs) and negatively regulated by BK potassium channels activated by Ca2+ influx through L-type VGCCs. We now show that at P4 and P6-P7, release is mediated by P/Q-, R- and L-type VGCCs. Interestingly, L-type VGCCs have a dual role: they both support release and fuel BK channels, suggesting that at immature stages presynaptic proteins involved in release are less compartmentalized.