RT Journal Article SR Electronic T1 Target Dependent Compartmentalization of the Co-release of Glutamate and GABA from the Mossy Fibers JF The Journal of Neuroscience JO J. Neurosci. FD Society for Neuroscience SP 1915-16 DO 10.1523/JNEUROSCI.1915-16.2016 A1 Emilio J. Galván A1 Rafael Gutiérrez YR 2016 UL http://www.jneurosci.org/content/early/2016/12/09/JNEUROSCI.1915-16.2016.abstract AB The mossy fibers (MF) co-release glutamate and GABA onto pyramidal cells of CA3 during development, until the end of the third postnatal week. However, the major target cells of the MF are the interneurons of CA3. Therefore, it has been shown that the interneurons of the hilus and Stratum lucidum receive this dual monosynaptic input on MF stimulation. Because plasticity of glutamatergic transmission from the different terminals of the MF is target-specific, we here asked whether co-release of glutamate and GABA was also subjected to a target-dependent compartmentalization. We analyzed the occurrence and plasticity of MF simultaneous glutamatergic-GABAergic signaling onto interneurons of the different strata of CA3 in rats during the third postnatal week. We show the co-existence of time-locked, monosynaptic glutamate receptor and GABA receptor-mediated synaptic responses evoked by MF stimulation in interneurons from S. lucidum and S. radiatum, but not in S. lacunosum-moleculare. As expected from transmission of MF origin, MF-GABAergic responses were depressed by activation of metabotropic glutamate receptors. Strikingly, while MF-glutamatergic responses underwent LTD, the simultaneous MF-GABAergic responses of S. lucidum interneurons, but not of S. radiatum, displayed a Hebbian form of LTP that was mimicked by PKC activation. PKA activation potentiated MF-glutamatergic responses of S. radiatum interneurons, whereas in S. lucidum interneurons only GABAergic responses were potentiated. We here disclose that the co-release of glutamate and GABA, as well as its plasticity are compartmentalized in a target-dependent manner, showing counter-balanced compensatory plasticity of two neurotransmitters released by different terminals of the same pathway.SIGNIFICANCE STATEMENTThe mossy fibers transiently co-release glutamate and GABA onto pyramidal cells of CA3. We here describe that they can also co-release these amino acids onto interneurons, in a target-dependent manner. Many interneurons in Stratum (S) lucidum and S. radiatum receive both signals, while those in S. lacunosum moleculare exclusively receive a glutamatergic signal. Noteworthy, glutamatergic LTD, known to exist on S. lucidum interneurons, coexists in the same pathway with a presynaptic form of GABAergic LTP, while interneurons of S. radiatum, despite receiving this dual signaling, do not display such plasticity. The GABAergic LTP is mimicked with PKA or PKC activation. We disclose compartmentalized co-release of glutamate and GABA and its differential plasticity from a single pathway onto different interneuron sets.