TY - JOUR
T1 - Electrophysiological, morphological, and topological properties of two histochemically distinct subpopulations of cerebellar unipolar brush cells
AU - Kim, Jin Ah
AU - Sekerková, Gabriella
AU - Mugnaini, Enrico
AU - Martina, Marco
N1 - Funding Information:
Animals This study was carried out on mice in accordance with the guidelines issued by the National Institutes of Health and the Society for Neuroscience to minimize the number of animals used and their suffering.
Funding Information:
Acknowledgments This work was supported by NIH grant RO1 09904. Paraffin embedding and sectioning of the paraffin-embedded blocks was performed by Northwestern University Mouse Histology and Phenotyping Laboratory, which is supported by a Cancer Center Support Grant (NCI CA060553). The authors wish to thank Drs. Joe P. Doyle, Joseph D. Dougherthy, and Nataniel Heintz, The Rockefeller University, New York, NY, for breeding pairs of Tg(Grp-EGFP)DV197 mice.
PY - 2012/12
Y1 - 2012/12
N2 - 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.
AB - 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.
KW - Calretinin
KW - GABAB
KW - GIRK
KW - MGluR1α
KW - Modulation .Vestibulocerebellum
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U2 - 10.1007/s12311-012-0380-8
DO - 10.1007/s12311-012-0380-8
M3 - Article
C2 - 22528965
AN - SCOPUS:84870455687
VL - 11
SP - 1012
EP - 1025
JO - Cerebellum
JF - Cerebellum
SN - 1473-4222
IS - 4
ER -