Unipolar brush cells form a glutamatergic projection system within the mouse cerebellar cortex

J Comp Neurol. 2001 Jun 4;434(3):329-41. doi: 10.1002/cne.1180.

Abstract

Unipolar brush cells (UBCs) of the mammalian vestibulocerebellum receive mossy fiber projections primarily from the vestibular ganglion and vestibular nuclei. Recently, the axons of UBCs have been shown to generate an extensive system of cortex-intrinsic mossy fibers, which resemble traditional cerebellar mossy fiber afferents and synapse with granule cell dendrites and other UBCs. However, the neurotransmitter used by the UBC axon is still unknown. In this study, we used long-term organotypic slice cultures of the isolated nodulus (lobule X) from postnatal day 8 mouse cerebella to identify the neurotransmitter and receptors at synapses of the UBC axon terminals, relying on the notion that, in these cultures, all of the cortex-extrinsic fibers had degenerated during the first few days in vitro. Quantification of glutamate immunogold labeling showed that the UBC axon terminals have the same high gold-particle density as the glutamatergic parallel fiber varicosities. Furthermore, UBCs identified by calretinin immunoreactivity expressed the glutamate receptor subunits GluR2/3, NMDAR1, and mGluR2/3, like they do in the mature mouse cerebellum in situ. Evoked excitatory postsynaptic currents (EPSCs), spontaneous EPSCs, and burst discharges were demonstrated in UBCs and granule cells by patch-clamp recording. Both the evoked and spontaneous EPSCs were blocked by ionotropic glutamate receptor antagonists CNQX and D-AP5. We conclude that neurotransmission at the UBC axon terminals is glutamatergic. Thus, UBCs provide a powerful network of feedforward excitation within the granular layer, which may amplify vestibular signals and synchronize activity in clusters of functionally related granule cells which project vertically to patches of Purkinje cells.

Publication types

  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • 2-Amino-5-phosphonovalerate / pharmacology
  • 6-Cyano-7-nitroquinoxaline-2,3-dione / pharmacology
  • Animals
  • Calbindin 2
  • Cell Size
  • Cerebellar Cortex / chemistry
  • Cerebellar Cortex / cytology*
  • Cerebellar Cortex / physiology*
  • Excitatory Amino Acid Antagonists / pharmacology
  • Excitatory Postsynaptic Potentials / drug effects
  • Excitatory Postsynaptic Potentials / physiology
  • Glutamic Acid / physiology*
  • Interneurons / chemistry
  • Interneurons / physiology*
  • Interneurons / ultrastructure
  • Mice
  • Mice, Inbred C57BL / anatomy & histology*
  • Microscopy, Immunoelectron
  • Nerve Fibers / chemistry
  • Nerve Fibers / physiology
  • Nerve Fibers / ultrastructure
  • Neural Pathways
  • Organ Culture Techniques
  • Patch-Clamp Techniques
  • Receptors, AMPA / analysis
  • Receptors, N-Methyl-D-Aspartate / analysis
  • S100 Calcium Binding Protein G / analysis
  • Tissue Embedding

Substances

  • Calb2 protein, mouse
  • Calbindin 2
  • Excitatory Amino Acid Antagonists
  • NMDA receptor A1
  • Receptors, AMPA
  • Receptors, N-Methyl-D-Aspartate
  • S100 Calcium Binding Protein G
  • glutamate receptor ionotropic, AMPA 3
  • Glutamic Acid
  • 6-Cyano-7-nitroquinoxaline-2,3-dione
  • 2-Amino-5-phosphonovalerate
  • glutamate receptor ionotropic, AMPA 2