NeuroNex News

February 2024, Issue #5

From the Lab

Here, we see cultured primary rat cortical neurons expressing a bioluminescent calcium indicator. NeuroNex researchers recently developed this method—referred to as CaBLAM—that relies on bioluminescence instead of the more traditional fluorescence-based calcium indicators to study changing levels of calcium in the brain. Image courtesy of Nathan Shaner.

Calcium is vital for cell function, and researchers have created tools to study how its levels change in cells. Typically, these tools have used fluorescence to monitor changes, however, scientists with the NeuroNex project, Bioluminescence for Optimal Brain Control and Imaging, recently developed a method to study these changes using bioluminescence. This new method––referred to as CaBLAM––is better than traditional fluorescent tools for some applications because it’s highly sensitive to calcium changes but doesn't need strong light, which cannot easily be supplied deep inside the body and can harm cells, to work. What’s more, CaBLAM can clearly show calcium activity in individual cells and small cell parts, especially in neurons, without disturbing those cells.

“Our new probe expands the possibilities for single-cell calcium activity imaging in deep tissues and light-sensitive cell types, and we expect future improvements to further enable observation of calcium dynamics during free behavior in more natural settings,” says Nathan Shaner, associate professor at the University of California, San Diego and Co-PI on the NeuroNex project. “We are now using CaBLAM in conjunction with a few unique fluorescent proteins to make ‘recorders’ of calcium signaling history that don’t require external excitation light, allowing them to be used non-invasively.”

As the team moves forward, they hope to engineer brighter versions of CaBLAM tuned to respond to a variety of calcium levels as well as expand the color palette of this sensor family and generate similar indicators for other biochemical activities.

Spotlight

In this virtual bee simulation, a bee’s brain shows changes in activity in response to recognized odors. Members of the Odor2Action Network recently developed this game as a way to get K-12 students interested in biology and animal behavior. Image credit: Bee Learning Lab

The Odor2Action network—an international group of 16 PIs and close to 75 researchers located across the US, UK, and Canada—is focused on examining how animals use information picked up from odors around them to guide their behavior.

Recently, Odor2Action researcher Brian Smith collaborated with Arizona State University’s Ask-A-Biologist Program to develop a virtual bee simulation that illustrates behavioral learning principles, focusing on conditioning bees to odors. In this game, players select an odor stimulus (orange or rose blossom, or none) and decide on rewarding the bee with varying concentrations of sugar water (affecting learning speed), or not at all, across eight trials. The game visually demonstrates changes in the bee's brain activity based on the chosen stimuli and rewards, offering an interactive learning experience on conditioning.

Building upon a previous NSF IdeasLab game that delved into bee navigation and communication, this new game is part of the team's broader research into learning and navigation.

“The games have been developed with the expressed intent of reaching out to K-12 students to get them interested in biology and animal behavior,” says Smith. “The games are interactive, so students can set different parameters to explore the consequences for the bee’s behavior. We also have been successful in reaching out to adults with this content.” The Odor2Action Network has also been examining ways in which this international, multidisciplinary group interacts with one another as they work on varied aspects of the project. They’re doing a social network analysis—using surveys to map relationships between members—to understand not only how well they communicate with each other but also how much they collaborate on research.

“As funding for team science and convergence research continues to grow, it’s important to understand what factors make large projects a success (or not),” says Kathryn Cochran, Odor2Action Project Manager. “Doing these surveys annually has helped us track how our efforts and connections change year to year, and help us identify where our strengths and weaknesses are in terms of transdisciplinary connections.” The group reviews the network graphs, discusses what patterns are emerging, and evaluates what changes they might wish to see in the year ahead.