Physicist’s Technique Could Transform Brain Mapping

UT Arlington physicist develops fiber-optic two-photon optogenetic stimulator to map neural interactions

A new research tool developed by Samarendra Mohanty, an assistant professor of physics at the University of Texas at Arlington, promises to help scientists map and monitor how neurons interact across different areas of the brain. The device is a compact fiber-optic, two-photon optogenetic stimulator that enables precise stimulation of light-sensitive proteins in living cells and neural tissue using near-infrared light.

The work, described in a paper published in Optics Letters, builds on Mohanty’s earlier finding that near-infrared light can activate light-responsive proteins introduced into cells and neurons. By combining two-photon excitation with fiber-optic delivery, this approach aims to provide higher spatial precision and deeper penetration than conventional single-photon optogenetic methods that use blue or green light.

The image shows a brain with light beams entering it.
Optogenetic stimulation uses light rather than electrical pulses to activate neurons, reducing tissue damage. This illustrative image is not directly connected to the research described.

Two-photon optogenetics involves introducing a gene for a light-sensitive protein—commonly referred to as ChR2—into excitable cells. When illuminated with a focused, low-energy near-infrared beam, those cells can be activated with exceptional spatial selectivity. Mohanty’s fiber-optic implementation delivers this two-photon excitation directly to tissue circuits, allowing researchers to stimulate a specific region and then observe responses both locally and in connected brain areas.

Mapping functional connections is a central goal for neuroscience. Physical wiring diagrams of the brain reveal anatomical links, but they do not explain how those links operate during behavior or sensory processing. Mohanty emphasizes that tools capable of precise, localized stimulation—and simultaneous readout of activity across neural networks—are essential to understand the dynamic function of brain circuits. In that context, two-photon optogenetic stimulation provides a means to control neurons while monitoring downstream effects within the network.

The technology may prove particularly useful for large-scale initiatives intended to chart brain function. Mohanty noted its potential relevance to the BRAIN initiative—Brain Research Through Advancing Innovative Neurotechnologies—a federal research effort supported during the Obama administration that included new investments to develop advanced tools for neuroscience. By enabling targeted activation of specific neural populations and tracking responses across linked areas, fiber-optic two-photon optogenetics could contribute to mapping how circuits produce behavior and cognition.

Advantages of Mohanty’s approach include reduced invasiveness and improved depth of access. Optogenetic stimulation avoids many forms of tissue damage associated with electrical stimulation because it relies on light to modulate neuronal activity rather than electrodes. Using near-infrared wavelengths for two-photon excitation also allows for deeper tissue penetration and more confined excitation volumes compared with visible light, leading to greater precision in activating individual cells or small groups of cells.

Another advance reported in the paper is the replacement of bulky microscope setups or complex scanning systems with a compact fiber-optic delivery platform. By delivering the two-photon beam through a fiber, the stimulator can be more readily combined with in vivo experiments and behavioral studies. Mohanty’s team is collaborating with Linda Perrotti, an assistant professor in the UT Arlington Department of Psychology, to test and refine the technology in living animals, with the goal of linking controlled neural activation to measurable behavioral outcomes.

“Scientists have mapped many of the brain’s physical connections, but understanding how those connections work requires tools that can precisely control and probe neuronal activity,” Mohanty said. “Two-photon optogenetics gives us that control and the ability to observe how circuits respond when a specific node is stimulated.”

Notes about this BRAIN mapping initiative and neuroscience research

The research team included Mohanty’s lab members Kamal Dhakal, Ling Gu, and Bryan Black.

Contact: Traci Peterson — UT Arlington

Source: UT Arlington press release

Image Source: The brain image is available in the public domain.

Original Research: Abstract for “Fiber-optic two-photon optogenetic stimulation” by Samarendra Mohanty, Kamal Dhakal, Ling Gu, and Bryan Black in Optics Letters. Published online May 7, 2013. DOI: unavailable.