Determinants of postsynaptic Ca²⁺ signaling in Purkinje neurons

Neuronal integration in Purkinje neurons involves many forms of Ca²⁺ signaling. Two afferent synaptic inputs, the parallel and the climbing fibers, provide a major drive for these signals. These two excitatory synaptic inputs are both glutamatergic. Postsynaptically they activate alpha-amino-3-hydroxy-5-methyl-4-propionic acid (AMPA) receptors (AMPARs) and metabotropic glutamate receptors (mGluRs). Unlike most other types of central neurons, Purkinje neurons do not express NMDA (N-methyl-D-aspartate) receptors (NMDARs). AMPARs in Purkinje neurons are characterized by a low permeability for Ca²⁺ ions. AMPAR-mediated synaptic depolarization may activate voltage-gated Ca²⁺ channels, mostly of the P/Q-type. The resulting intracellular Ca²⁺ signals are shaped by the Ca²⁺ buffers calbindin and parvalbumin. Ca²⁺ clearance from the cytosol is brought about by Ca²⁺-ATPases in the plasma membrane and the endoplasmic reticulum, as well as the Na⁺ -Ca²⁺-exchanger. Binding of glutamate to mGluRs induces postsynaptic Ca²⁺-transients through two G protein-dependent pathways: involving (1) the release of Ca²⁺ ions from intracellular Ca²⁺ stores and (2) the opening of the cation channel TRPC1. Homer proteins appear to play an important role in postsynaptic Ca²⁺ signaling by providing a direct link between the plasma membrane-resident elements (mGluRs and TRPC1) and their intracellular partners, including the IP₃Rs.