mGluR1 Regulates the Interspike Interval Threshold for Dendritic Ca2+ Transients in the Cerebellar Purkinje Cells.

Abstract

Ca²⁺+ transients can be observed in the distal dendrites of Purkinje cells (PCs) despite their lack of action potential backpropagation. These Ca²⁺+ events in distal dendrites require specific patterns of PC firing, such as complex spikes (CS) or simple spikes (SS) of burst mode. Unlike CS, which can act directly on voltage-gated calcium channels in the dendrites through climbing fiber inputs, the condition that can produce the Ca²⁺+ events in distal dendrites with burst mode SS is poorly understood. Here, we propose the interspike interval threshold (ISIT) for Ca²⁺+ transients in the distal dendrites of PC. We found that to induce the Ca²⁺+ transients in distal dendrites the frequency of spike firing of PC should reach 250 Hz (3 ms ISI). Metabotropic glutamate receptor 1 (mGluR1) activation significantly relieved the ISIT and established cellular conditions in which spike firing with 50 Hz (19 ms ISI) could induce Ca²⁺+ transients in the distal dendrites. In contrast, blocking T-type Ca²⁺+ channels or depleting the endoplasmic reticulum Ca²⁺+ store resulted in a stricter condition in which spike firing with 333 Hz (2 ms ISI) was required. Our findings demonstrate that the PC has strict ISIT for dendritic Ca²⁺+ transients, and this ISIT can be relieved by mGluR1 activation. This strict restriction of ISIT could contribute to the reduction of the signal-to-noise ratio in terms of collecting information by preventing excessive dendritic Ca²⁺+ transients through the spontaneous activity of PC.