AMPA Receptors in NG2 Glia Differently Affect Signal Transduction in the Hippocampus and Cerebellum

Gray matter NG2 glia constitute a heterogeneous population of cells whose functions remain incompletely understood. In the hippocampus, Schaffer collaterals activate AMPA receptors (AMPARs) in NG2 glia, giving rise to small excitatory post-synaptic currents (EPSCs). Climbing fibers of the cerebellum also form synapses with NG2 glia, although producing much larger EPSCs. We aimed to identify mechanisms generating these regional differences in the efficacy of neuron-glia synapses. Combined patch-clamp and RT-PCR analyses allowed for determining structural and functional differences of AMPARs expressed by the glial cells. Comparing pharmacological and molecular data in both regions revealed stronger expression of Ca²⁺ permeable AMPARs in cerebellar NG2 glia. Different expression patterns were found both for AMPAR subunits and their auxiliary proteins. Moreover, experiments using the low-affinity AMPAR antagonist γ-DGG pointed towards higher synaptic glutamate concentrations at cerebellar synapses, likely due to multivesicular release, which contributed to enhanced synaptic efficacy. Finally, we examined short-term plasticity and showed that pre- and postsynaptic mechanisms contributed to paired-pulse depression at climbing fiber-NG2 glia synapses. Together, our data provide new insights into the molecular and functional specialization of NG2 glia and improve our understanding of the mechanisms underlying neuron-glia synaptic signaling, by highlighting how region-specific differences in AMPAR composition and presynaptic release properties shape this communication in the central nervous system.