Dynamic Metabotropic Control of Intrinsic Firing in Cerebellar Unipolar Brush Cells

Abstract

Neuronal firing is regulated by the complex interaction of multiple depolarizing and hyperpolarizing currents; intrinsic firing, which defines the neuronal ability to generate action potentials in the absence of synaptic excitation, is particularly sensitive to modulation by currents that are active below the action potential threshold. Cerebellar unipolar brush cells (UBCs) are excitatory granule layer interneurons that are capable of intrinsic firing; here we show that, in acute mouse cerebellar slices, barium-sensitive background potassium channels of UBCs effectively regulate intrinsic firing. We also demonstrate that these channels are regulated by group II metabotropic glutamate receptors (mGluRs), which we show to be present in both of the known subsets of UBCs, one of which expresses calretinin and the other mGluR1α. Finally, we show that background potassium currents controlling UBCs' firing are mediated by at least two channel types, one of which is sensitive and the other insensitive to the GIRK blocker tertiapin. Thus in UBCs, glutamatergic transmission appears to have a complex bimodal effect: although it increases spontaneous firing through activation of ionotropic receptors, it also has inhibitory effects through the mGluR-dependent activation of tertiapin-sensitive and -insensitive background potassium currents.