ABSTRACT
The distribution and role of zinc ions in the CNS have been studied for many years, particularly with regard to neurons. Zinc is present and essential in the brain, and indeed, throughout the body, in two main forms: tightly bound to metalloproteins, including many enzymes and zinc finger transcription factors, and free or loosely bound. The latter, histochemically reactive or chelatable zinc, represents only a fraction of the total in any given region, and its function and regulation are poorly understood. Typically, this “free” or chelatable Zn2+ is present in vesicles within cells, and in the brain, appears largely restricted in a subset of glutamatergic neurons (i.e., “gluzinergic29) located principally in the telencephalon. This distribution is the basis of the well-known pattern obtained by the so-called Danscher-Timms or autometallographic methods, which highlight the very dense concentration of Zn2+ (and indirectly, glutamate) in the mossy fibers of the dentate gyrus of the hippocampus, amygdala, and neocortex among other areas (Figure 22.1). More precisely, zinc is present in glutamate-containing synaptic vesicles and released during neuronal activity,28,29 though its physiological function is still debated. What is known is that extracellular Zn2+ can modulate the activity of several ion channels, most notably those activated by NMDA, AMPA, and GABA receptors.11,51,91,95 Chelatable, or more specifically, synaptic zinc, has also been shown to participate in the experimental induction of LTP.49
