IPSPs strongly inhibit climbing fiber-activated [Ca2+]i increases in the dendrites of cerebellar Purkinje neurons.

The interaction between the excitatory climbing fiber (CF) response and stellate cell inhibition was studied in guinea pig Purkinje cells in sagittal slices from the cerebellar vermis. Sharp microelectrode recordings from the soma or dendrites were combined with high-speed fluorescence imaging of intracellularly injected fura-2. In this way both the electrical responses and the associated [Ca2+]i changes could be monitored at the same time. Usually simultaneously activated inhibition caused almost no change to the somatically recorded CF response. However, the inhibition caused a strong reduction in the CF-associated [Ca2+]i increase which normally was widespread in the dendrites. This effect was graded; stronger inhibition caused a larger and more widespread reduction in the [Ca2+]i change that was greatest in the more distal dendrites. Sometimes the reduction was over 90% in the distal dendrites and occasionally it was localized to only a single dendritic branch. Both the inhibitory postsynaptic potential (IPSP) and the associated reduction in the CF-induced [Ca2+]i change were blocked by bicuculline, a GABAA receptor antagonist. Dendritic recordings showed that each CF response evoked a 2-3 msec wide action potential. The amplitude of this action potential was reduced in a graded manner by the IPSP in parallel with the reduction in the [Ca2+]i change. Varying the time between the activation of the IPSP and the CF response showed that both the reduction in the [Ca2+]i change and the action potential amplitude occurred in a narrow time window of about 8-10 msec, about the rise time of the IPSP. Together these results indicate that the CF response activates a fast dendritic Ca2+ spike that causes most of the [Ca2+]i increase, both of which can be blocked by an inhibitory shunting conductance. This interaction provides a means whereby Ca(2+)-dependent dendritic mechanisms can be modulated without affecting the immediate output of the Purkinje cell.