Elsevier

Neuroscience

Volume 98, Issue 4, July 2000, Pages 625-636
Neuroscience

Unipolar brush cell: a potential feedforward excitatory interneuron of the cerebellum

https://doi.org/10.1016/S0306-4522(00)00123-8Get rights and content

Abstract

Unipolar brush cells are a class of interneurons in the granular layer of the mammalian cerebellum that receives excitatory mossy fiber synaptic input in the form of a giant glutamatergic synapse. Previously, it was shown that the unipolar brush cell axon branches within the granular layer, giving rise to large terminals. Single mossy fiber stimuli evoke a prolonged burst of firing in unipolar brush cells, which would be distributed to postsynaptic targets within the granular layer. Knowledge of the ultrastructure of the unipolar brush cell terminals and of the cellular identity of its postsynaptic targets is required to understand how unipolar brush cells contribute to information processing in the cerebellar circuit. To investigate the unipolar brush cell axon and its targets, unipolar brush cells were patch-clamped in fresh parasagittal slices from rat cerebellar vermis with electrodes filled with Lucifer Yellow and Biocytin, and examined by confocal fluorescence and electron microscopy. Biocytin was localized with diaminobenzidine chromogen or gold-conjugated, silver-intensified avidin. Light microscopic examination revealed a single thin axon emanating from the unipolar brush cell soma that gave rise to 2–3 axon collaterals terminating in mossy fiber-like rosettes in the granular layer, typically within a few hundred μm of the soma. In some cases, axon collaterals crossed the white matter within the same folium before terminating in the adjacent granular layer. Electron microscopic examination of serial ultrathin sections revealed that proximal unipolar brush cell axons and axon collaterals were unmyelinated and devoid of synaptic contacts. However, the rosette-shaped enlargements of each collateral formed the central component of glomeruli where they were surrounded by dendrites of granule cells and/or other unipolar brush cells, with which they formed asymmetric synaptic contacts. A long-latency repetitive burst of polysynaptic activity was observed in granule cells in this cerebellar region following white matter stimulation. The unipolar brush cell axons, therefore, form a system of cortex-intrinsic mossy fibers.

The results indicate that synaptic excitation of unipolar brush cells by mossy fibers will drive a large population of granule cells, and thus will contribute a powerful form of distributed excitation within the basic circuit of the cerebellar cortex.

Section snippets

Experimental procedures

Young male and female Sprague–Dawley rats purchased from a commercial breeder were used for this investigation. All efforts were made to minimize both the suffering and the number of animals used. All experiments conformed to protocols approved by the Northwestern University Center for Experimental Animal Resources (CEAR), an AAALAC-accredited facility, and followed guidelines issued by the National Institutes of Health and the Society for Neuroscience.

Morphology of intracellularly labeled unipolar brush cells

More than 50 physiologically identified, Lucifer Yellow/Biocytin-filled UBCs were screened by light and electron microscopy and were selected for this study if the tracer appeared strictly intracellular and ultrastructure was well preserved. Eleven UBCs that met these criteria were subjected to further analysis. Three of these were stained with the DAB chromogen and eight with gold-conjugated avidin followed by silver intensification. All the UBCs in the sample were obtained from 15–28-day-old

Discussion

In this paper, we provide the first demonstration that UBC axon terminals target multiple granule cell dendrites and also brush dendrioles of other UBCs. We confirm that the UBC brush participates in a glomerular array where its dendrioles are innervated by a mossy fiber rosette, and demonstrate that branched UBC axons form rosette-shaped endings occupying glomeruli within the granule cell layer of the mammalian cerebellum. The UBC axons form asymmetric small synaptic junctions with granule

Acknowledgements

This study was supported by National Institutes of Health Grants NS-09904 (E.M.), NS-34840 (N.T.S.) and DC-002764 (N.T.S. and E.M.). We are grateful to Dr Linda Overstreet for providing the recording illustrated in Fig. 2, to Dr David Rossi for participation in preliminary experiments, and to Dr Simon Alford for assistance with confocal microscopy.

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    ‡

    Present address: Department of Physiology, West China University of Medical Sciences, Chemgdu, Sichuan 610041, P.R. China

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