Electrophysiological, morphological, and topological properties of two histochemically distinct subpopulations of cerebellar unipolar brush cells

Unipolar brush cells (UBCs) are excitatory cerebellar granular layer interneurons whose brush-like dendrites receive one-to-one mossy fiber inputs. Subclasses of UBCs differ primarily by expressing metabotropic glutamate receptor (mGluR) 1α or calretinin. We used GENSAT Tg(Grp-EGFP) BAC transgenic mice, which selectively express enhanced green fluorescent protein (EGFP) in mGluR1α-positive UBCs to compare the functional properties of the two subclasses. Compared to EGFP-negative UBCs, which include the calretininpositive cells, EGFP-positive UBCs had smaller somata (area 48 vs 63 μm²), lower specific membrane resistance (6.4 vs. 13.7 Kω cm²), were less prone to intrinsic firing, and showed more irregular firing (in cell-attached ∼49 % were firing vs. ∼88 %, and the CV was 0.53 vs. 0.32 for EGFPnegative cells). Some of these differences are attributable to higher density of background K⁺ currents in EGFP-positive cells (at -120 mV, the barium-sensitive current was 94 vs. 37 pA in EGFP-negative cells); Ih, on the contrary, was more abundantly expressed in EGFP-negative cells (at -140 mV, it was -122 vs. -54 pA in EGFP-positive neurons); furthermore, while group II mGluR modulation of the background potassium current in EGFP-negative UBCs wasmaintained after intracellular dialysis, mGluR modulation in EGFP-positive UBCs was lost in whole-cell recordings. Finally, cell-attached firing was reversibly abolished by the GABAB activation in EGFP-positive, but not in EGFPnegative UBCs. Immunohistochemistry showed that EGFPnegative UBCs express GIRK2 at high density, while mGluR1α UBCs are GIRK2 negative, suggesting that GIRK2 mediates the mGluR-sensitive current in EGFPnegative UBCs. These data suggest that the two subclasses perform different functions in the cerebellar microcircuits.