Glial cells in the brain express neurotransmitter receptors and can respond appropriately to application of exogenous neurotransmitters such as glutamate. However, activation of receptors by endogenous, synaptically released transmitter has been difficult to demonstrate directly. Using cell- pair recording in cerebellar cultures from embryonic mouse, it is shown that activation of a cerebellar granule neuron can give rise to a rapid inward current in an adjacent glial cell. This current is mediated by activation of Ca2+-permeable AMPA/kainate receptors and is largely independent of glutamate reuptake or gap junctional coupling. Furthermore, prolonged stimulation of the granule neuron at 4 Hz can give rise to long-term potentiation (LTP) of the glial synaptic current that has similar properties to LTP of granule neuron-Purkinje neuron synaptic transmission-its induction is independent of postsynaptic depolarization, postsynaptic Ca2+ influx, or glutamate receptor activation but requires presynaptic Ca2+ influx. These findings suggest a model in which cerebellar LTP is both induced and expressed presynaptically and therefore may be detected by either neuronal or glial postsynaptic cells.
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