Developmental regulation of nicotinic synapses on cochlear inner hair cells

KATZ E; ELGOYHEN AB; GOMEZ CASATI ME; KNIPPER M; VETTER D; FUCHS P; GLOWATZKI E

J Neuroscience

Año: 2004 vol. 24 p. 7814 - 7820

1529-2401

In the mature cochlea, inner hair cells (IHCs) transduce acoustic signals into receptor potentials, communicating to the brain by synaptic contacts with afferent fibers. Before the onset of hearing, a transient efferent innervation is found on IHCs. This inhibitory synapse is mediated by a nicotinic cholinergic receptor containing the a9 and a10 subunits. Calcium influx through that receptor activates nearby calcium-dependent (SK2-containing) channels. This inhibitory synapse disappears at the onset of hearing, about postnatal day 12. We studied this developmental transition using whole cell recordings from IHCs in acutely excised apical turns of the rat organ of Corti. Acetylcholine (ACh) elicited ionic currents in 88-100% of the cells between P3 and P14, but in only 1 of 11 cells at P16-22. Potassium depolarization of efferent terminals caused inhibitory postsynaptic currents (IPSCs) in 67% of IHCs at P3, in 93-100% of cells from P7 to P12, but in only 40 % of cells by P13 and in none of the cells tested between P16-22. Although earlier work had shown that the á9 subunit is expressed in adult IHCs, in situ hybridization and antibody labeling showed expression of the a10 receptor subunit in IHCs only from P3 to P13; by P21 á10 mRNA and immunoreactivity were undetectable. Antibodies to the SK2 channel that subserves the synaptic K+ current showed a similar time course of expression. The correlated expression of these proteins with functional innervation suggests that the Alpha10 and SK2 genes, but not the Alpha9, are regulated by synaptic activity.