Target-Dependent Compartmentalization of the Corelease of Glutamate and GABA from the Mossy Fibers

Abstract

The mossy fibers (MFs) corelease 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 the plasticity of glutamatergic transmission from the different terminals of the MF is target specific, we here asked whether the corelease 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 coexistence of time-locked, glutamate receptor and GABA receptor-mediated mono synaptic responses evoked by MF stimulation in interneurons from stratum lucidum and stratum radiatum, but not in interneurons from stratum lacunosum-moleculare. As expected from the transmission of MF origin, MF GABAergic responses were depressed by the activation of metabotropic glutamate receptors. Strikingly, while MF glutamatergic responses underwent LTD, the simultaneous MF GABAergic responses of stratum lucidum interneurons, but not of stratum radiatum interneurons, displayed a Hebbian form of LTP that was mimicked by PKC activation. PKA activation potentiated MF glutamatergic responses of stratum radiatum interneurons, whereas in stratum lucidum interneurons only GABAergic responses were potentiated. We here disclose that the corelease of glutamate and GABA, as well as their plasticity are compartmentalized in a target-dependent manner, showing counterbalanced compensatory plasticity of two neurotransmitters released by different terminals of the same pathway.

Large scale analysis of the diversity and complexity of the adult spinal cord neurotransmitter typology

“…Interestingly, we also found that spinal cord neurons exhibit extensive co-expression of glutamate and GABA -two neurotransmitters with opposing functions. Although we did not investigate the release of these transmitters in this work, the possible co-release of glutamate and GABA from single nerve terminals in the brain has been demonstrated extensively ( Beltrán and Gutiérrez, 2012;Galván and Gutiérrez, 2017;Noh et al, 2010;Root et al, 2014;Shabel et al, 2014;Yoo et al, 2016). Our findings support the existence of multitransmitter neurons in the zebrafish spinal cord, as was already established in the lamprey spinal cord (Fernández-López et al, 2012) and the mammalian brain (Granger et al, 2017;Tritsch et al, 2016).…”

Large-Scale Analysis of the Diversity and Complexity of the Adult Spinal Cord Neurotransmitter Typology

“…Interestingly, we also found that spinal cord neurons exhibit extensive co-expression of glutamate and GABA, two neurotransmitters with opposing functions. Although we did not investigate the release of these transmitters in this work, the possible co-release of glutamate and GABA from single nerve terminals in the brain has been demonstrated extensively (Beltrán and Gutiérrez, 2012, Galván and Gutiérrez, 2017, Noh et al., 2010, Root et al., 2014, Shabel et al., 2014, Yoo et al., 2016). Our findings support the existence of multi-transmitter neurons in the zebrafish spinal cord, as was already established in the lamprey spinal cord (Fernández-López et al., 2012) and the mammalian brain (Granger et al., 2017, Tritsch et al., 2016).…”

Short-term plasticity at cerebellar granule cell to molecular layer interneuron synapses expands information processing

“…In most of cases, synaptic efficacy among boutons issued from a single axon varies with the identity of the postsynaptic cell (Blackman et al, 2013; Markram et al, 1998). Target-cell-dependent heterogeneity relies on differences in the probability of release (Koester and Johnston, 2005), responsiveness to neuromodulators (Buchanan et al, 2012; Delaney and Jahr, 2002; Pelkey et al, 2006; Scanziani et al, 1998) or the ability to co-release GABA and glutamate (Galván and Gutiérrez, 2017). Target-cell-dependent STP has also been described at cerebellar GC-MLI synapses by using stimulation of beam of PFs or clusters of GC somata; upon high-frequency stimulation, compound synaptic responses exhibit a facilitating profile at GC-SC synapses whereas these responses depress at GC-BC synapses (Bao et al, 2010).…”