• Rebecca F Krall, Thanos Tzounopoulos, and Elias Aizenman.
• Department of Neurobiology, University of Pittsburgh School of Medicine, USA; Department of Otolaryngology, University of Pittsburgh School of Medicine, USA; Pittsburgh Hearing Research Center, University of Pittsburgh School of Medicine, USA; Pittsburgh Institute for Neurodegenerative Diseases, University of Pittsburgh School of Medicine, USA.
• Neuroscience. 2021 Mar 1; 457: 235-258.

AbstractNearly sixty years ago Fredrich Timm developed a histochemical technique that revealed a rich reserve of free zinc in distinct regions of the brain. Subsequent electron microscopy studies in Timm- stained brain tissue found that this "labile" pool of cellular zinc was highly concentrated at synaptic boutons, hinting a possible role for the metal in synaptic transmission. Although evidence for activity-dependent synaptic release of zinc would not be reported for another twenty years, these initial findings spurred decades of research into zinc's role in neuronal function and revealed a diverse array of signaling cascades triggered or regulated by the metal. Here, we delve into our current understanding of the many roles zinc plays in the brain, from influencing neurotransmission and sensory processing, to activating both pro-survival and pro-death neuronal signaling pathways. Moreover, we detail the many mechanisms that tightly regulate cellular zinc levels, including metal binding proteins and a large array of zinc transporters.Copyright © 2021 IBRO. Published by Elsevier Ltd. All rights reserved.

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