Rapid, biochemical tagging of cellular activity history in vivo
bioRxiv – September 06, 2023
Source: medRxiv/bioRxiv/arXiv
Summary
Cells use calcium signals to communicate, essential for many biological processes. A new method quickly tags active cells with elevated calcium levels in living animals without invasive procedures. This innovative approach allows for immediate tracking of cellular activity, revealing insights into brain responses, such as those triggered by psilocybin.
Abstract
Intracellular calcium (Ca2+) is ubiquitous to cell signaling across all biology. While existing fluorescent sensors and reporters can detect activated cells with elevated Ca2+ levels, these approaches require implants to deliver light to deep tissue, precluding their noninvasive use in freely-behaving animals. Here we engineered an enzyme-catalyzed approach that rapidly and biochemically tags cells with elevated Ca2+ in vivo. Ca2+-activated Split-TurboID (CaST) labels activated cells within 10 minutes with an exogenously-delivered biotin molecule. The enzymatic signal increases with Ca2+ concentration and biotin labeling time, demonstrating that CaST is a time-gated integrator of total Ca2+ activity. Furthermore, the CaST read-out can be performed immediately after activity labeling, in contrast to transcriptional reporters that require hours to produce signal. These capabilities allowed us to apply CaST to tag prefrontal cortex neurons activated by psilocybin, and to correlate the CaST signal with psilocybin-induced head-twitch responses in untethered mice.