Do We Need Zinc to Think?

Chelatable Zn2+, which is found in the synaptic vesicles of certain glutamatergic neurons in several regions of the forebrain, is released during neuronal activity. Zn2+ exhibits numerous effects on ligand-gated and voltage-dependent ion channels, and released Zn2+ is therefore likely able to modulate synaptic transmission. The physiologically relevant actions of Zn2+, however, have remained unclear. Recent research exploiting improved Zn2+-sensitive optical probes has suggested some intriguing effects for synaptically released Zn2+, including heterosynaptic regulation of N-methyl-D-aspartate (NMDA) receptor function, and a novel role as a trans-synaptic second messenger that may enter postsynaptic neurons to modulate various signal transduction pathways.