GABA regulates the release of acetylcholine (ACh) at the medial olivocochlear (MOC) efferent-outer hair cell synapse through presynaptic GABAB receptors.

WEDEMEYER C; ZORRILA DE SAN MARTIN J; TORBIDONI AV; BETTLER B; ELGOYHEN AB; KATZ E

Buenos Aires

Congreso; 5th General Conference of the Society for Neurochemistry; 2012

Outer hair cells (OHCs) of the mammalian cochlea are innervated by MOC efferent fibers. These OHC-MOC synapses are formed before the onset of hearing and maintained throughout the life of the animal. Although acetylcholine (ACh) is the main neurotransmitter, ã-aminobutiric acid (GABA) is also present at MOC synaptic terminals. We  have  previously  shown  that  GABA  modulates  the  cholinergic  input  at  MOC-inner hair cell (IHCs) synapses  by  acting on presynaptic GABAB receptors. To further evaluate the role of the GABAB in the modulation of ACh release in MOC-OHC synapses, synaptic currents evoked by electrically stimulating the efferent fibers were recorded in voltage-clamped OHCs from isolated mouse organs of Corti at postnatal days 9-14. Preliminary results shows that the quantal content of evoked release was increased by the GABAB antagonist CGP35348 (1µM) (111.2 ± 22.1%, n=4 p<0.05). These results, together with the lack of effect of this drug on spontaneous synaptic current amplitude, suggest that GABA exerts a negative control on synaptic transmission through presynaptic GABAB receptors at MOC-OHC synapse, resembling MOC-IHC transient synapses. To confirm this hypothesis, we are now evaluating the effects of CGP35348 on GABAB knock-out (KO) mice and whether P/Q or N-type Ca2+ channels, that support release at this synapse, are the targets of GABAB receptor activation.