A genetically encoded far-red fluorescent indicator for imaging synaptically released Zn2

Sci Adv. 2023 Mar;9(9):eadd2058. doi: 10.1126/sciadv.add2058. Epub 2023 Mar 1.

Abstract

Synaptic zinc ion (Zn2+) has emerged as a key neuromodulator in the brain. However, the lack of research tools for directly tracking synaptic Zn2+ in the brain of awake animals hinders our rigorous understanding of the physiological and pathological roles of synaptic Zn2+. In this study, we developed a genetically encoded far-red fluorescent indicator for monitoring synaptic Zn2+ dynamics in the nervous system. Our engineered far-red fluorescent indicator for synaptic Zn2+ (FRISZ) displayed a substantial Zn2+-specific turn-on response and low-micromolar affinity. We genetically anchored FRISZ to the mammalian extracellular membrane via a transmembrane (TM) ⍺ helix and characterized the resultant FRISZ-TM construct at the mammalian cell surface. We used FRISZ-TM to image synaptic Zn2+ in the auditory cortex in acute brain slices and awake mice in response to electric and sound stimuli, respectively. Thus, this study establishes a technology for studying the roles of synaptic Zn2+ in the nervous system.

MeSH terms

  • Animals
  • Auditory Cortex*
  • Brain
  • Cell Membrane
  • Coloring Agents
  • Mammals
  • Mice
  • Zinc

Substances

  • Coloring Agents
  • Zinc