Dendritic calcium signaling triggered by spontaneous and sensory-evoked climbing fiber input to cerebellar Purkinje cells in vivo.

Cerebellar Purkinje cells have one of the most elaborate dendritic trees in the mammalian CNS, receiving excitatory synaptic input from a single climbing fiber (CF) and from ∼200,000 parallel fibers. The dendritic Ca(2+) signals triggered by activation of these inputs are crucial for the induction of synaptic plasticity at both of these synaptic connections. We have investigated Ca(2+) signaling in Purkinje cell dendrites in vivo by combining targeted somatic or dendritic patch-clamp recording with simultaneous two-photon microscopy. Both spontaneous and sensory-evoked CF inputs triggered widespread Ca(2+) signals throughout the dendritic tree that were detectable even in individual spines of the most distal spiny branchlets receiving parallel fiber input. The amplitude of these Ca(2+) signals depended on dendritic location and could be modulated by membrane potential, reflecting modulation of dendritic spikes triggered by the CF input. Furthermore, the variability of CF-triggered Ca(2+) signals was regulated by GABAergic synaptic input. These results indicate that dendritic Ca(2+) signals triggered by sensory-evoked CF input can act as associative signals for synaptic plasticity in Purkinje cells in vivo and may differentially modulate plasticity at parallel fiber synapses depending on the location of synapses, firing state of the Purkinje cell, and ongoing GABAergic synaptic input.