Efferent inhibition of immature inner hair cells and its modulation by metabotropic glutamate receptors.

JUAN D. GOUTMAN; GASTON C. SENDIN; TOBIAS MOSER; ELISABETH GLOWATZKI

Baltimore, MD, USA

Congreso; XXIX ARO MidWinter Meeting; 2006

Inner hair cells (IHC) in the mammalian cochlea receive transient efferent innervation that disappears after the onset of hearing.  These efferent synapses mediate inhibitory postsynaptic currents (IPSCs) through acetylcholine receptors and sK potassium channel activation.  Quantal parameters of these synapses were studied by electrical stimulation of efferent axons and whole cell recordings from IHCs in excised apical turns of the rat cochlea (P7-12) (Goutman et al., 2005).  At a holding potential of -90 mV, a quantal size of -18 pA was estimated from the amplitude distribution of spontaneous IPSCs, and a quantum content of 1 was calculated by different methods including failures and coefficient of variation.  IPSC amplitude distributions showed multiple peaks following Poisson statistics, suggesting that more than one vesicle could be released. The low probability of release observed in stimulation protocols with frequencies between 0.25 – 1 Hz was increased by the application of metabotropic glutamate receptor (mGluRs) agonists, either the non-subtype specific t-ACPD (100 mM, n = 7), or the mGluR type I specific DHPG (50 and 100 mM, n = 4).  A clear reduction in the failure rate and a shift to higher values in the amplitude distribution of evoked IPSCs was observed, while the quantal size remained constant.  The mean IPSC amplitude was more than 200 % larger during the application of the mGluR agonists compared to control.  These results suggest a presynaptic locus of action for the mGluRs agonists.  Application of the glutamate transporter blocker TBOA (200 mM) increased spontaneous efferent release, raising the possibility that spilled-over glutamate released at the IHC afferent synapse might activate mGluRs (n = 4). Our results suggest that glutamate released at the IHC afferent synapse may activate a feedback loop that strengthens the action of transient efferent synapses onto IHCs through the activation of mGluRs.