Modulation of ACh release at the efferent-IHC synapse by presynaptic GABAB receptors

WEDEMEYER , C; BALLESTERO, J.; ZORRILLA DE SAN MART¨ªN, J.; KATZ, E.; ELGOYHEN, A.B

Huerta Grande C¨®rdoba- Argentina

Congreso; 1er Reunion Conjunta Taller-SAN; 2009

Sociedad Argentina de Investigacion en Neurociencias (SAN) y Taller de Neurociencias

Modulation of ACh release at the efferent-IHC synapse by presynaptic GABAB receptors Carolina Wedemeyer, Jimena Ballestero, Javier Zorrilla de San Martin, Ana Bel¨¦n Elgoyhen, Eleonora Katz (ekatz@dna.uba.ar) Instituto de Investigaciones en Ingenier¨ªa Gen¨¦tica y Biolog¨ªa Molecular - INGEBI (CONICET) Before the onset of hearing, inner hair cells (IHCs) of the mammalian cochlea are transiently innervated by medial olivocohlear (MOC) efferent fibers. This synapse is cholinergic, inhibitory and mediated by the ¦Á9¦Á10 nicotinic receptor. Although ACh is the main transmitter released at this synapse, there is evidence showing that GABA is present at MOC synaptic terminals. However, no GABAergic currents have been recorded so far in IHCs. Moreover, the possibility that synaptically released GABA could be modulating the cholinergic input at MOC-synapses by acting on presynaptic GABAB receptors has not been investigated yet.  In the present work, we evaluated the effects of two modulators of GABAB receptors on the quantal content of transmitter release at the MOC-IHC synapse. Postsynaptic currents, evoked by electrically stimulating the efferent fibers, were recorded in voltage-clamped (-90 mV) IHCs from acutely isolated mouse organs of Corti. Quantal content was significantly increased by the antagonist CGP35348 at 1mM (55 +/- 19 % p < 0.05) and significantly decreased by 1mM of the agonist Baclofen (68 +/- 8 % p <0.001). Our results suggest GABA might be exerting a negative feedback control on the release of ACh through presynaptic GABAB receptors.