A role for zinc in cerebellar synaptic transmission?

There is considerable evidence that the transition metal zinc plays an important role in mammalian neural development, physiology and pathology. The most compelling evidence for a synaptic role for zinc comes from hippocampal studies: zinc is concentrated in the synaptic vesicles of some glutamatergic neurons, zinc can be released during neural activity and zinc can modulate postsynaptic GABA and glutamate receptors. The possibility that zinc is involved in cerebellar synaptic transmission is supported by the expression of specific zinc transporters (ZnT, including the synaptic vesicle transporter ZnT-3) in the cerebellar cortex. Furthermore, some subtypes of neurotransmitter receptors, expressed by cerebellar neurones, are highly sensitive to low concentrations of exogenous zinc. However there appears to be little chelatable (synaptic) zinc in the cerebellum, deletion of the ZnT-3 gene has no effect on motor phenotype and there is currently no evidence that zinc is released from cerebellar neurones to have physiological actions. Thus it is possible that the different types of zinc transporter found in the cerebellum play a neuroprotective rather than a signalling role.