Data from: 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 is also
affected by the expression of GlyT2, leading to a 56 % decrease in
relative charge. Acute manipulations of cytosolic GABA and glycine supply
recapitulate the modulation of IPSC charge, supporting the hypothesis that
presynaptic loading of glycine negatively impact the GABAergic
transmission in mixed interneurons through a competition for vesicular
filling. Our results suggest that heterogeneity of neurotransmitter supply
within the GoC class may provide a presynaptic mechanism to tune the gain
of the stereotypic granular layer microcircuit, thereby expanding the
realm of possible dynamic behavior.