The origin of physiological local mGluR1 supralinear Ca2+ signals in cerebellar Purkinje neurons

Abstract

In Purkinje neurons, the climbing fibre (CF) input provides a signal to parallel fibre (PF) synapses triggering PF synaptic plasticity. This supralinear Ca2+ signal, co-localised with the PF Ca2+ influx, occurs when PF activity precedes the CF input. Using membrane potential (Vm) and Ca2+ imaging, we identified the biophysical determinants of these supralinear Ca2+ signals. The CF-associated Ca2+ influx is mediated by T-type or by P/Q-type Ca2+ channels, depending on whether the dendritic Vm is hyperpolarised or depolarised. The resulting Ca2+ elevation is locally amplified by saturation of the endogenous Ca2+ buffer produced by the PF-associated Ca2+ influx, in particular by the slow Ca2+ influx mediated by type-1 metabotropic glutamate receptors (mGluR1s). When the dendrite is hyperpolarised, mGluR1s boost neighbouring T-type channels providing a mechanism for local coincident detection of PF-CF activity. In contrast, when the dendrite is depolarised, mGluR1s increase dendritic excitability by inactivating A-type K+ channels, but this phenomenon is not restricted to the activated PF synapses. Thus, Vm is likely a crucial parameter in determining PF synaptic plasticity and the occurrence of hyperpolarisation episodes is expected to play an important role in motor learning.