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

Jin Ah Kim, Gabriella Sekerkova, Enrico Mugnaini, Marco Martina*

*Corresponding author for this work

Research output: Contribution to journalArticle

16 Citations (Scopus)

Abstract

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.

Original languageEnglish (US)
Pages (from-to)1012-1021
Number of pages10
JournalCerebellum
Volume11
Issue number4
DOIs
StatePublished - Dec 1 2012

Fingerprint

Metabotropic Glutamate Receptors
enhanced green fluorescent protein
Calbindin 2
Carisoprodol
Patch-Clamp Techniques
Interneurons
Barium
Dendrites
Transgenic Mice
Dialysis
Potassium
Immunohistochemistry
Neurons
Membranes
metabotropic glutamate receptor type 1

Keywords

  • Calretinin
  • GABAB
  • GIRK
  • MGluR1α
  • Modulation .Vestibulocerebellum

ASJC Scopus subject areas

  • Neurology
  • Clinical Neurology

Cite this

@article{e8a298820d2d4039a0f542ad85729905,
title = "Electrophysiological, morphological, and topological properties of two histochemically distinct subpopulations of cerebellar unipolar brush cells",
abstract = "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.",
keywords = "Calretinin, GABAB, GIRK, MGluR1α, Modulation .Vestibulocerebellum",
author = "Kim, {Jin Ah} and Gabriella Sekerkova and Enrico Mugnaini and Marco Martina",
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Electrophysiological, morphological, and topological properties of two histochemically distinct subpopulations of cerebellar unipolar brush cells. / Kim, Jin Ah; Sekerkova, Gabriella; Mugnaini, Enrico; Martina, Marco.

In: Cerebellum, Vol. 11, No. 4, 01.12.2012, p. 1012-1021.

Research output: Contribution to journalArticle

TY - JOUR

T1 - Electrophysiological, morphological, and topological properties of two histochemically distinct subpopulations of cerebellar unipolar brush cells

AU - Kim, Jin Ah

AU - Sekerkova, Gabriella

AU - Mugnaini, Enrico

AU - Martina, Marco

PY - 2012/12/1

Y1 - 2012/12/1

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.

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KW - GIRK

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KW - Modulation .Vestibulocerebellum

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