Comprehensive Summary
Mei et al. developed a new family of fluorescent sensors (TympGn) to monitor glutamate (Glu), the brain’s primary excitatory neurotransmitter, in real time. Applying a novel host–guest interaction technique, they evaluated ten versions and concluded that TympG2 proved to be the most effective. TympG2 exhibited glutamate selectivity versus other amino acids, fast response times (approx. 145 ms), and good stability. Using this probe, the researchers were able to gauge glutamate concentrations within various cellular regions including the plasma membrane, cytoplasm, and mitochondria, where hypoxia induced sharply elevated levels. For imaging deep parts of the brain they also used TympG2, in tissue sections and zebrafish. Most significantly, they generated the first map of the activity of glutamate in 24 brain regions in live mice and found that hypoxia reduces the connectivity among the cortex, hippocampus, and thalamus.
Outcomes and Implications
Glutamate is critical for brain function, but too much of it can result in problems like stroke damage, depression, Alzheimer’s disease, and Parkinson’s disease. Current methods have great difficulty measuring rapid changes in glutamate or changes in certain cell and brain regions. TympG2 overcomes these limitations to provide a quicker and more robust method to investigate the role of glutamate in health and disease. This work reveals new details of how neurological diseases happen, by showing how hypoxia alters glutamate levels and disrupts brain networks. It's still relatively new; however, TympG2 may one day provide a direction into diagnostics and therapies for diseases which are connected with unbalanced glutamate.