Activation of presynaptic GABA(B(1a,2)) receptors inhibits synaptic transmission at mammalian inhibitory cholinergic olivocochlear-hair cell synapses.

CAROLINA WEDEMEYER; JAVIER ZORRILLA DE SAN MARTÍN; JIMENA BALLESTERO; MARÍA EUGENIA GO´MEZ-CASATI; ANA VANESA TORBIDONI; PAUL A. FUCHS; BERNHARD BETTLER; ANA BELEN ELGOYHEN; ELEONORA KATZ

JOURNAL OF NEUROSCIENCE

SOC NEUROSCIENCE

Lugar: Washington; Año: 2013 vol. 33 p. 15477 - 15487

0270-6474

The synapse between olivocochlear (OC) neurons and cochlear mechanosensory hair cells is cholinergic, fast, and inhibitory. The inhib- itory sign of this cholinergic synapse is accounted for by the activation of Ca2􏰀-permeable postsynaptic 􏰉9􏰉10 nicotinic receptors coupled to the opening of hyperpolarizing Ca2􏰀-activated small-conductance type 2 (SK2)K􏰀 channels. Acetylcholine (ACh) release at this synapse is supported by both P/Q- and N-type voltage-gated calcium channels (VGCCs). Although the OC synapse is cholinergic, an abundant OC GABA innervation is present along the mammalian cochlea. The role of this neurotransmitter at the OC efferent innervation, however, is for the most part unknown. We show that GABA fails to evoke fast postsynaptic inhibitory currents in apical developing inner and outer hair cells. However, electrical stimulation of OC efferent fibers activates presynaptic GABAB(1a,2) receptors [GABAB(1a,2)Rs] that downregulate the amount of ACh released at the OC? hair cell synapse, by inhibiting P/Q-type VGCCs. We confirmed the expression of GABABRs at OC terminals contacting the hair cells by coimmunostaining for GFP and synaptophysin in transgenic mice expressing GABAB1?GFP fusion proteins. Moreover, coimmunostaining with antibodies against the GABA synthetic enzyme glutamic acid decar- boxylase and synaptophysin support the idea that GABA is directly synthesized at OC terminals contacting the hair cells during develop- ment. Thus, we demonstrate for the first time a physiological role for GABA in cochlear synaptic function. In addition, our data suggest that the GABAB1a isoform selectively inhibits release at efferent cholinergic synapses.