Researchers at University of California Davis have developed a fast, noninvasive tool called Ca2+-activated Split-TurboID (CaST) to track which neurons and biomolecules are activated by psychedelic drugs.
Published in Nature Methods, this protein-based tool could help scientists explore the benefits of psychedelics for treating brain disorders like depression and PTSD. Psychedelics such as LSD, DMT, and psilocybin promote neuron growth and connection in the brain’s prefrontal cortex.
Christina Kim, a UC Davis neurology professor, emphasizes the need to understand how psychedelics affect cells to design safer versions. The new CaST tool helps scientists track the molecular processes behind psychedelics’ benefits quickly, taking just 10 to 30 minutes instead of the usual hours. This could advance research on the positive effects of these compounds.
“We created proteins in the lab that are delivered into neurons using harmless viruses. Once inside, the proteins start working.” Kim explained.
The research, led by Kim and David Olson, uses the CaST tool to track neuron activity by monitoring calcium levels, a standard marker of neuron activity. When neurons are active, they have high calcium levels, which CaST uses to tag the cells with a small molecule called biotin.
In the study, Kim and her team gave mice psilocybin. They used the CaST tool with biotin to find neurons with increased calcium in the prefrontal cortex, an area affected by many brain disorders. They also observed head-twitch responses, which indicate psychedelic-induced hallucinations.
CaST helps study freely moving animals, unlike other methods that require the mouse’smouse’s head to be fixed. Biotin, used in tagging, allows easy detection with existing tools. This experiment provided a “snapshot” of the prefrontal cortex areas activated by psilocybin.
Kim and her team are working on using the CaST tool for brain-wide cellular labeling and enhancing the details of proteins produced by neurons affected by psychedelics. They plan to analyze these proteins at the UC Davis Proteomics Core Facility to compare psilocybin-treated animals with controls and disease models.
The goal is to understand how psychedelics improve brain disorder symptoms. Kim also hopes to compare psychedelic effects with those of non-hallucinogenic treatments. CaST will be key for studying these neurotherapeutic drugs.
The new method allows scientists to quickly track how psychedelics affect neurons, providing valuable insights into their effects on the brain. This technique helps researchers understand the cellular processes behind the benefits of psychedelics, potentially leading to better treatments for brain disorders.
Journal reference :
- Zhang, R., Anguiano, M., Aarrestad, I.K. et al. Rapid, biochemical tagging of cellular activity history in vivo. Nature Methods. DOI: 10.1038/s41592-024-02375-7.
