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The Journal of Neuroscience, July 13, 2005, 25(28):6490-6498; doi:10.1523/JNEUROSCI.1500-05.2005

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Cellular/Molecular
Target-Dependent Use of Coreleased Inhibitory Transmitters at Central Synapses

Guillaume P. Dugué,^1 * Andréa Dumoulin,^2 * Antoine Triller,² and Stéphane Dieudonné¹

¹Laboratoire de Neurobiologie Moléculaire et Cellulaire, Centre National de la Recherche Scientifique, Unité Mixte de Recherche 8544, and ²Laboratoire de Biologie Cellulaire de la Synapse, Institut National de la Santé et de la Recherche Médicale U497, École Normale Supérieure, 75005 Paris, France

Corelease of GABA and glycine by mixed neurons is a prevalent mode of inhibitory transmission in the vertebrate hindbrain. However, little is known of the functional organization of mixed inhibitory networks. Golgi cells, the main inhibitory interneurons of the cerebellar granular layer, have been shown to contain GABA and glycine. We show here that, in the vestibulocerebellum, Golgi cells contact both granule cells and unipolar brush cells, which are excitatory relay interneurons for vestibular afferences. Whereas IPSCs in granule cells are mediated by GABA_A receptors only, Golgi cell inhibition of unipolar brush cells is dominated by glycinergic currents. We further demonstrate that a single Golgi cell can perform pure GABAergic inhibition of granule cells and pure glycinergic inhibition of unipolar brush cells. This specialization results from the differential expression of GABA_A and glycine receptors by target cells and not from a segregation of GABA and glycine in presynaptic terminals. Thus, postsynaptic selection of coreleased fast transmitters is used in the CNS to increase the diversity of individual neuronal outputs and achieve target-specific signaling in mixed inhibitory networks.

Key words: GABA; glycine; corelease; vestibular system; cerebellum; inhibition

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Received Jan 4, 2005; revised May 27, 2005; accepted May 28, 2005.

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