Neurotransmitter content heterogeneity within an interneuron class shapes inhibitory transmission at a central synapse

Neurotransmitter content is deemed the most basic defining criterion for neuronal classes, contrasting with the intercellular heterogeneity of many other molecular and functional features. Here we show, in the adult mouse brain, that neurotransmitter content variegation within a neuronal class is a component of its functional heterogeneity. Most Golgi cells (GoCs), the well-defined class of cerebellar interneurons inhibiting granule cells (GrCs), contain cytosolic glycine, accumulated by the neuronal transporter GlyT2, and GABA in various proportions. To assess the functional consequence of this neurotransmitter variation, we paired GrCs recordings with optogenetic stimulations of single GoCs, which preserve the intracellular transmitter mixture. We show that the strength and decay kinetics of GrCs IPSCs, which are entirely mediated by GABAA receptors are negatively correlated to the presynaptic expression of GlyT2 by GoCs. We isolate a slow spillover component of GrCs inhibition that i...