Activation of presynaptic GABA(B(1a,2)) receptors inhibits synaptic transmission at mammalian inhibitory cholinergic olivocochlear-hair cell synapses
JournalArticle (Originalarbeit in einer wissenschaftlichen Zeitschrift)
 
ID 2833431
Author(s) Wedemeyer, C.; Zorrilla de San Martin, J.; Ballestero, J.; Gomez-Casati, M. E.; Torbidoni, A. V.; Fuchs, P. A.; Bettler, B.; Elgoyhen, A. B.; Katz, E.
Author(s) at UniBasel Bettler, Bernhard
Year 2013
Title Activation of presynaptic GABA(B(1a,2)) receptors inhibits synaptic transmission at mammalian inhibitory cholinergic olivocochlear-hair cell synapses
Journal Journal of Neuroscience
Volume 33
Number 39
Pages / Article-Number 15477-15487
Abstract The synapse between olivocochlear (OC) neurons and cochlear mechanosensory hair cells is cholinergic, fast, and inhibitory. The inhibitory sign of this cholinergic synapse is accounted for by the activation of Ca(2+)-permeable postsynaptic alpha9alpha10 nicotinic receptors coupled to the opening of hyperpolarizing Ca(2+)-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 GABA(B(1a,2)) receptors [GABA(B(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 GABA(B)Rs at OC terminals contacting the hair cells by coimmunostaining for GFP and synaptophysin in transgenic mice expressing GABA(B1)-GFP fusion proteins. Moreover, coimmunostaining with antibodies against the GABA synthetic enzyme glutamic acid decarboxylase and synaptophysin support the idea that GABA is directly synthesized at OC terminals contacting the hair cells during development. Thus, we demonstrate for the first time a physiological role for GABA in cochlear synaptic function. In addition, our data suggest that the GABA(B1a) isoform selectively inhibits release at efferent cholinergic synapses.
Publisher Society for Neuroscience
ISSN/ISBN 0270-6474 ; 1529-2401
edoc-URL http://edoc.unibas.ch/dok/A6338710
Full Text on edoc Available
Digital Object Identifier DOI 10.1523/JNEUROSCI.2554-13.2013
PubMed ID http://www.ncbi.nlm.nih.gov/pubmed/24068816
Document type (ISI) Article
 
   

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