Mobile zinc as a modulator of sensory perception

Abstract

Mobile zinc is an abundant transition metal ion in the central nervous system, with pools of divalent zinc accumulating in regions of the brain engaged in sensory perception and memory formation. Here, we present essential tools that we developed to interrogate the role(s) of mobile zinc in these processes. Most important are (a) fluorescent sensors that report the presence of mobile zinc and (b) fast, Zn‐selective chelating agents for measuring zinc flux in animal tissue and live animals. The results of our studies, conducted in collaboration with neuroscientist experts, are presented for sensory organs involved in hearing, smell, vision, and learning and memory. A general principle emerging from these studies is that the function of mobile zinc in all cases appears to be downregulation of the amplitude of the response following overstimulation of the respective sensory organs. Possible consequences affecting human behavior are presented for future investigations in collaboration with interested behavioral scientists.

Caged Zn2+ Photolysis in Zebrafish Whole Brains Reveals Subsecond Modulation of Dopamine Uptake

“…Zn 2+ is presynaptically released from select populations of glutamatergic neurons in the hippocampus, amygdala, striatum, and thalamus, − resulting in transiently increased synaptic (100–300 μM) and extracellular (10–20 μM) Zn 2+ levels . Zn 2+ that is released in the striatum diffuses to the densely innervating dopaminergic terminals. , There, it can modulate dopamine (DA) levels through several avenues, including modifying vesicular fusion pore formation and directly inhibiting DA uptake through an allosteric binding site on the DA transporter (DAT) .…”

Nobel symposium #168 Visions of bio‐inorganic chemistry: metals and the molecules of life

“…The answer lies in both specific and general control mechanisms such as chaperones and a strict maintenance of metal availability. Lippard provides an intriguing perspective of how mobile zinc influences the amplitude of sensory response in the central nervous system [15]. Analytical tools in the form of Zn 2+ -specific chelators that have been developed to study these processes and effects are also described.…”