Purkinje cells labelled with anti-Calbindin (blue), NG2+ cells labelled with anti-NG2 antibodies (green), and a climbing fibre labelled with Alexa-488 dextran (red) in the rat cerebellar cortex. Image courtesy of S. C. Lin, H. Nishiyama and D. E. Bergles, Department of Neuroscience, Johns Hopkins University School of Medicine, Baltimore, USA.

Climbing fibres (CFs) from the inferior olive, one of the two main inputs to the cerebellum, make direct synaptic contacts with the cerebellum's output neurons, Purkinje cells. A new study shows that CFs also form conventional glutamatergic synapses with a population of glia in the cerebellar cortex. These glial cells, which express the proteoglycan NG2, might have an important part to play in the control of cerebellar function by CF inputs.

NG2-expressing (NG2+) glia are oligodendrocyte precursor cells that are found throughout the developing and mature CNS. In the cerebellar cortex, they extend many processes around Purkinje cell dendrites. Like Bergmann glia, which ensheath excitatory synapses on Purkinje cells, NG2+ cells express ionotropic glutamate receptors. But whereas Bergmann glia express uptake sites for glutamate and can, therefore, limit the spread of this neurotransmitter, NG2+ cells do not express glutamate transporters. What is the role of NG2+ cells in the cerebellum?

Lin and colleagues made whole-cell recordings from NG2+ cells in mouse cerebellar slices. These non-excitable cells responded to CF stimulation with a transient inward current mediated by calcium-permeable AMPA (α-amino-3-hydroxy-5-methyl-4-isoxazole propionic acid) receptors. The response seemed to be due to glutamate release at a conventional synapse rather than ectopic release, having rapid rise and decay kinetics and being remarkably stable with repeated stimulation. Paired recordings of Purkinje cells and NG2+ cells showed that one CF can provide input to both cell types; however, unlike Purkinje cells, NG2+ cells were found to receive input from more than one CF.

In an electron microscopic analysis, conventional synaptic junctions were seen between CFs and the processes of physiologically characterized NG2+ cells. Synapses on NG2+ cells were not wrapped by Bergmann glia, but the processes of NG2+ cells were found in direct apposition with Bergmann glial lamellae.

The cerebellum is involved in a range of motor and cognitive functions, but whether all aspects of the CF control of these functions can be attributed to the innervation of Purkinje cells has been unclear. Whereas Bergmann glia respond to the ectopic release of glutamate from CF terminals and are thought to isolate CF–Purkinje cell synapses, Lin et al. have shown that NG2+ glial cells receive direct synaptic inputs from CFs and are well placed to influence cerebellar signalling. But the precise role of NG2+ cells remains elusive. In future studies it will be important to determine whether rapid signalling between CFs and NG2+ glia can affect the fate of these progenitor cells or the activity of surrounding neurons.