α2δ-2 is required for depolarization-induced suppression of excitation in purkinje cells

alpha 2 delta proteins (CACNA2D1-4) are required for normal neurological function and contribute to membrane trafficking of voltage-gated calcium channels, through which calcium entry initiates numerous physiological processes. However, it remains unclear how alpha 2 delta proteins influence calcium-mediated signalling to control neuronal output. Using whole-cell recordings of mouse Purkinje cells, we show that alpha 2 delta-2 is required for functional coupling of postsynaptic voltage-dependent calcium entry with calcium-dependent effector mechanisms controlling two different outputs, depolarization-induced suppression of excitation and spike afterhyperpolarization. Our findings indicate an important role for alpha 2 delta-2 proteins in regulating functional postsynaptic calcium channel coupling in neurons, providing new context for understanding the effects of alpha 2 delta mutations on neuronal circuit function and presenting additional potential avenues to manipulate alpha 2 delta-mediated signalling for therapeutic gain.

Automated summary

The study shows that alpha2δ-2 protein plays a crucial role in influencing the coupling of postsynaptic voltage-dependent calcium channels in neurons, affecting neuronal output regulation.