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Related Experiment Video

Updated: Aug 8, 2025

Real-Time Fluorescent Measurement of Synaptic Functions in Models of Amyotrophic Lateral Sclerosis

Real-Time Fluorescent Measurement of Synaptic Functions in Models of Amyotrophic Lateral Sclerosis

Published on: July 16, 2021

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

Tianchen Wu¹, Manoj Kumar², Jing Zhang¹

¹Department of Molecular Physiology and Biological Physics, and Center for Membrane and Cell Physiology, University of Virginia School of Medicine, Charlottesville, VA 22908, USA.

Science Advances

|March 1, 2023

Summary

Researchers developed a new far-red fluorescent indicator, FRISZ-TM, to track synaptic zinc (Zn²⁺) dynamics in the brain. This tool enables real-time monitoring of zinc in awake animals, advancing neuroscience research.

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Published on: May 25, 2011

Area of Science:

Neuroscience
Molecular Biology
Biochemistry

Background:

Synaptic zinc ions (Zn²⁺) play a crucial role as neuromodulators in the brain.
Understanding the physiological and pathological roles of synaptic Zn²⁺ is limited by the lack of effective research tools for in vivo tracking.

Purpose of the Study:

To develop a novel genetically encoded fluorescent indicator for real-time monitoring of synaptic Zn²⁺ dynamics.
To establish a new technology for investigating the functions of synaptic Zn²⁺ in the nervous system.

Main Methods:

Engineered a far-red fluorescent indicator for synaptic Zn²⁺ (FRISZ) with a Zn²⁺-specific turn-on response and low-micromolar affinity.
Genetically anchored FRISZ to the mammalian extracellular membrane using a transmembrane (TM) ⍺ helix, creating the FRISZ-TM construct.
Characterized FRISZ-TM at the mammalian cell surface and utilized it for imaging synaptic Zn²⁺ in brain slices and awake mice.

Main Results:

The developed FRISZ-TM indicator demonstrated a significant Zn²⁺-specific turn-on response.
FRISZ-TM successfully imaged synaptic Zn²⁺ dynamics in the auditory cortex of acute brain slices and awake mice.
The indicator responded to both electric and sound stimuli, highlighting its utility in functional studies.

Conclusions:

This study successfully developed and validated FRISZ-TM, a novel tool for monitoring synaptic Zn²⁺.
FRISZ-TM provides a valuable technological advancement for studying the roles of synaptic zinc in neurological processes.
The developed indicator facilitates research into the physiological and pathological significance of synaptic Zn²⁺ in the nervous system.