Mechanisms and functional roles of glutamatergic synapse diversity in a cerebellar circuit

Synaptic currents display a large degree of heterogeneity of their temporal characteristics, but the functional role of such heterogeneities remains unknown. We investigated in rat cerebellar slices synaptic currents in Unipolar Brush Cells (UBCs), which generate intrinsic mossy fibers relaying vestibular inputs to the cerebellar cortex. We show that UBCs respond to sinusoidal modulations of their sensory input with heterogeneous amplitudes and phase shifts. Experiments and modeling indicate that this variability results both from the kinetics of synaptic glutamate transients and from the diversity of postsynaptic receptors. While phase inversion is produced by an mGluR2-activated outward conductance in OFF-UBCs, the phase delay of ON UBCs is caused by a late rebound current resulting from AMPAR recovery from desensitization. Granular layer network modeling indicates that phase dispersion of UBC responses generates diverse phase coding in the granule cell population, allowing climbing-fiber-driven Purkinje cell learning at arbitrary phases of the vestibular input. DOI: http://dx.doi.org/10.7554/eLife.15872.001
eLife digest Whether walking, riding a bicycle or simply standing still, we continually adjust our posture in small ways to prevent ourselves from falling. Our sense of balance depends on a set of structures inside the inner ear called the vestibular system. These structures detect movements of the head and relay this information to the brain in the form of electrical signals. A brain area called the vestibulo-cerebellum then combines these signals with sensory input from the eyes and muscles, before sending out further signals to trigger any adjustments necessary for balance. One of the main cell types within the vestibulo-cerebellum is the unipolar brush cell (or UBC for short). UBCs pass on signals to another type of neuron called Purkinje cells, which support the learning of motor skills such as adjusting posture. Zampini, Liu et al. set out to test the idea that UBCs transform inputs from the vestibular system into a format that makes it easier for cerebellar Purkinje cells to drive this kind of learning. First, recordings from slices of rodent brain revealed that UBCs respond in highly variable ways to vestibular input, with both the size and timing of responses varying between cells. This is because vestibular signals trigger the release of a chemical messenger called glutamate onto UBCs, but UBCs possess a variety of different types of glutamate receptors. Vestibular input therefore activates distinct signaling cascades from one UBC to the next. According to a computer model, this variability in UBC responses ensures that a subset of UBCs will always be active at any point during vestibular input. This in turn means that Purkinje cells can fire at any stage of a movement, which boosts the learning of motor skills. The next steps will be to test this hypothesis using mutant mice that lack specific receptor subtypes in UBCs or UBCs completely. A further challenge for the future will be to build a computer model of the vestibulo-cerebellar system that includes all of its component cell types. DOI: http://dx.doi.org/10.7554/eLife.15872.002