Microscopy is all about tradeoffs between the size of an imaged volume and spatial and temporal resolution. That is, until now. A new microscopy technique invented by researchers at the University of Vienna and MIT allows scientists to comprehensively image the neural firings of a living flatworm brain in realtime, vastly increasing the amount of data we can collect.
This is the first time a microscopy technique has been used to measure neural activity in an entire animal in realtime before. The principle behind its operation is similar to how the “bullet time” sequence in The Matrix was filmed, but with all the cameras returning data at the same time, and the sample being transparent.
In the filming of The Matrix, a series of cameras around Keanu Reeves captured his movements as he falls dramatically backwards, dodging bullets while the camera angle spins around him. A light field microscope is similar. It’s like a normal optical microscope, but it consists of a series of microlenses which beam back optical data from different angles around the sample in realtime. Later on, a powerful computer uses a sophisticated algorithm to reconstruct a high-resolution 3D model. The light field microscope already existed before this; the breakthrough was the reconstruction algorithm.
Prior to this, 3D imaging approaches were limited by the amount of time it takes for microscopes sophisticated enough to capture an entire flatworm at once to scan. Usually, this would be about ten times a second. The new approach operates at 50 Hz, or 50 times a second. This is fast enough to pick up all the nuances of neural activity in the densely packed flatworm brain. The axial spatial precision is up to 1.4 microns.
The light field microscope is relatively affordable, and the algorithm will now be used in behavioral studies of flatworms. This will allow researchers to expose the flatworms to precise stimuli and record their exact neural responses. It brings us closer to creating an exhaustive simulation, or algorithm representing the flatworm itself. The paper calls it, “tools for non-invasive interrogation of neuronal circuits with high spatio-temporal resolution.”
A longer-range objective will be to create an imaging system with such a wide field of view that it can observe the flatworm in a free-moving environment, rather than in just one place, as it is now. With the right improvements, the same principle could even be used to observe the neural activity of a population of interacting flatworms. The technique could also be used to observe other small, transparent organisms, such as zebrafish larvae.
A Stanford project previously created a high-resolution light field microscope for imaging the neural activity of an entire small organism, but it did not have a high enough frame rate to observe all the activity in realtime. The online updates for this project ended in 2008. Now, thanks to MIT and University of Vienna researchers, their original vision has been achieved.
Hopefully, these principles will be extended to observe larger and more complicated organisms. Pretty soon we could be looking at the cognitive algorithms of small animals in a much clearer way, and elucidating key details on the fundamentals of cognition. The time of full-brain dynamic circuit-mapping of neural processes is nigh!