TY - JOUR T1 - The Origin of Physiological Local mGluR1 Supralinear Ca<sup>2+</sup> Signals in Cerebellar Purkinje Neurons JF - The Journal of Neuroscience JO - J. Neurosci. SP - 1795 LP - 1809 DO - 10.1523/JNEUROSCI.2406-19.2020 VL - 40 IS - 9 AU - Karima Ait Ouares AU - Marco Canepari Y1 - 2020/02/26 UR - http://www.jneurosci.org/content/40/9/1795.abstract N2 - In mouse cerebellar Purkinje neurons (PNs), the climbing fiber (CF) input provides a signal to parallel fiber (PF) synapses, triggering PF synaptic plasticity. This signal is given by supralinear Ca2+ transients, associated with the CF synaptic potential and colocalized with the PF Ca2+ influx, occurring only when PF activity precedes the CF input. Here, we unravel the biophysical determinants of supralinear Ca2+ signals associated with paired PF-CF synaptic activity. We used membrane potential (Vm) and Ca2+ imaging to investigate the local CF-associated Ca2+ influx following a train of PF synaptic potentials in two cases: (1) when the dendritic Vm is hyperpolarized below the resting Vm, and (2) when the dendritic Vm is at rest. We found that supralinear Ca2+ signals are mediated by type-1 metabotropic glutamate receptors (mGluR1s) when the CF input is delayed by 100–150 ms from the first PF input in both cases. When the dendrite is hyperpolarized only, however, mGluR1s boost neighboring T-type channels, providing a mechanism for local coincident detection of PF-CF activity. The resulting Ca2+ elevation is locally amplified by saturation of endogenous Ca2+ buffers produced by the PF-associated Ca2+ influx via the mGluR1-mediated nonselective cation conductance. In contrast, when the dendritic Vm is at rest, 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 hyperpolarization episodes is expected to play an important role in motor learning.SIGNIFICANCE STATEMENT In Purkinje neurons, parallel fiber synaptic plasticity, determined by coincident activation of the climbing fiber input, underlies cerebellar learning. We unravel the biophysical mechanisms allowing the CF input to produce a local Ca2+ signal exclusively at the sites of activated parallel fibers. We show that when the membrane potential is hyperpolarized with respect to the resting membrane potential, type-1 metabotropic glutamate receptors locally enhance Ca2+ influx mediated by T-type Ca2+ channels, and that this signal is amplified by saturation of endogenous buffer also mediated by the same receptors. The combination of these two mechanisms is therefore capable of producing a Ca2+ signal at the activated parallel fiber sites, suggesting a role of Purkinje neuron membrane potential in cerebellar learning. ER -