Functional integration of calcium regulatory mechanisms at Purkinje neuron synapses

Abstract

Cerebellar Purkinje neurons receive synaptic inputs from three different sources: the excitatory parallel fibre and climbing fibre synapses as well as the inhibitory synapses from molecular layer stellate and basket cells. These three synaptic systems use distinct mechanisms in order to generate Ca(2+) signals that are specialized for specific modes of neurotransmitter release and post-synaptic signal integration. In this review, we first describe the repertoire of Ca(2+) regulatory mechanisms that generate and regulate the amplitude and timing of Ca(2+) fluxes during synaptic transmission and then explore how these mechanisms interact to generate the unique functional properties of each of the Purkinje neuron synapses.

Fig. 1.

a Schematic of a cerebellar Purkinje neuron (PN, blue) with its main synapses, the excitatory climbing fibre input from the inferior olive (CF-PN, red), the excitatory parallel fibre input from the cerebellar granule cells (PF-PN, light red), and the inhibitory synapses (IS-PN, green) from the stellate and basket cell inhibitory interneurones. b Calcium regulatory mechanisms within the different synapse compartments are shown; colours correspond to the colour used for the different synapses in a. VGCC voltage-gated calcium channel, PMCA plasma membrane calcium ATPase, NCX sodium calcium exchanger, NCKX sodium calcium potassium dependent exchanger, RyR ryanodine receptor, InsP ₃ -R inositol trisphosphate receptor, NMDA-R N-methyl-d-aspartate receptor, mGluR metabotropic glutamate receptor sub-type, CB calbindin, PV parvalbumin, Clr calretinin