Receptor occupancy limits synaptic depression at climbing fiber synapses

Postsynaptic responses to presynaptic stimulation are used regularly to assess the amount of transmitter released from presynaptic release zones. At climbing fiber-to-Purkinje cell synapses, the number of vesicles released per active zone follows changes in release probability such that, normally, more than one vesicle is released per presynaptic action potential. This leads to high occupation of postsynaptic AMPA receptors by glutamate and thus may render the postsynaptic response relatively insensitive to changes in release. We find that paired-pulse depression of presynaptic release is not accurately represented by postsynaptic responses because of receptor saturation. By lowering vesicular glutamate concentrations or by using nonsaturated Bergmann glial AMPA receptors to monitor presynaptic release, we find that presynaptic depression of release is much greater than suggested previously. In addition, densely expressed glutamate transporters can shield Bergmann glial AMPA receptors and presynaptic metabotropic glutamate receptors from activation.