Brain Mapping Seeks New Paths

New imaging techniques could build new roadways in neural mapping and provide a better understanding of how the brain functions.

A team at Columbia University — along with researchers from Cornell University, the California Institute of Technology and several technology companies — is now working on the development of such imaging techniques as part of the federal initiative called BRAIN (Brain Research through Advancing Innovative Neurotechnologies). They agree that photonics will ultimately play a key role in treating brain-related debilitating diseases and conditions.

One approach the researchers have explored would join a spatial light modulator (SLM)-based illumination system and a wavefront-coded imaging system. The SLM can excite neurons at various focal points and defined locations almost simultaneously; the imaging system can collect light from all focal points simultaneously.

Imaging of neuronal activity. Courtesy of Columbia University.

The SLM combined with the wavefront-coded system could form the basis of an imaging microscope that could image active neural networks in 3-D rather than 2-D, as with traditional optical microscopy techniques.

However, this simultaneous imaging capability is in its infancy, said Rafael Yuste of Columbia University, a lead researcher whose neuronal imaging activity and advocacy of an interdisciplinary Brain Activity Map Project have helped form the basis of the BRAIN program.

He cited recent work in which this new technique allowed the imaging of 50 neurons simultaneously, but said this could be improved.

“We hope that with better lasers and refinements, we will at some point be able to [simultaneously] image tens of thousands, if not hundreds of thousands, of neurons in 3-D," he said.

Currently, much of neuron mapping work uses standard laser sources developed for the semiconductor industry. Yuste says researchers need lasers that are tailored more closely to their own purposes. He noted that while the existing platform for imaging neural networks switches at 500 Hz, SLMs may need to switch at 10 kHz to perform this in 3-D.

Developing new imaging techniques for hi-res network-level maps of neuronal activity has met challenges, according to the researchers, including how to image the dynamic voltage activity accompanying neuronal activity.

At present, neurons are seen via a calcium imaging technique, which is too indirect and too slow to monitor brain activity.

“Instead, we need methods to image the voltage: to use photons to read out the voltage of membrane potential in neurons,” Yuste said.

This, too, presents challenges, as signal-to-noise ratios for voltage imaging are as much as 100 times worse than those seen for calcium imaging. However, researchers are developing potential solutions, such as organic molecules that act as voltage indicators, genetically encoded indicators for voltage, or means-based on quantum optics.

For more information, visit www.whitehouse.gov/share/brain-initiative.