Imaging Neural Systems: A Faster, More Sensitive Sensor

By Aloha Das, Amadou Diallo, Kayla Saychien

Neurons require changing calcium concentrations to fire allowing neuron firing in the brain to be imaged by isolating calcium ion flows. Previous calcium imaging methods lacked the speed and sensitivity to image neurons efficiently so this paper introduces a new variation of “sensor” molecule to detect these calcium ions that is significantly faster and more sensitive than previous such molecules.

Calcium ions are an integral part of neural firing patterns and their concentration gradients often shift between “on” and “off” states. Scientists  use genetically encoded calcium indicators (GECIs) to detect neurons firing since calcium ions play a major role in how neurons fire. GCaMP,  is a green fluorescent protein-based sensor that is genetically placed into organisms and fluoresces green when in the presence of calcium. The previous sensor models, jGCaMp6 and jGcaMP7,  were able to measure single action potential under favorable conditions and activity-induced calcium changes in small synaptic compartments such as dendritic spines  and axons. This paper introduces a new sensor called jGCaMP8 with different variants including slow, medium, and fast based on their decay times. The main important metrics for these sensors are sensitivity (how much signal is outputted by a given amount of neural firing) and speed (how long it takes for a given neural firing to reach and decay from peak signal), broken up into half-rise and half-decay times. 

Previous versions of jGCaMP have demonstrably lower sensitivity to calcium signals across both mouse and fly neurons. They also have overall higher half-rise and half-decay times, meaning the resultant signal would be more noisy since distinct neurons firing would not give a distinct enough signal. With better neural population imaging techniques, neuroscientists can easily perform studies with far greater accuracy which allows for better data extraction with less noise. This would facilitate better characterization and identification of neural disorders as well as a better understanding of mechanisms of important cognitive functions anywhere from memory storage to consciousness. Further refinements to jGCaMP8 would doubtless be welcome, but the significant improvement over the previous thread of GECIs such as jGCaMP7 and GCaMP6 makes a substantial contribution in this direction.

Citations

Zhang, Y., Rózsa, M., Liang, Y. et al. Fast and sensitive GCaMP calcium indicators for imaging neural populations. Nature 615, 884–891 (2023). https://doi.org/10.1038/s41586-023-05828-9