Research Area I: Optical Methods for Neuroscience

From BRAIN 2025: A Scientific Vision

Integrated Optical Approaches: Neuroscience and Instrumentation

Optical methods capture the central vision of the BRAIN Initiative, that of integrating many approaches into a single experiment. Optical methods can be multiplexed to combine activity monitoring, manipulation, circuit reconstruction, and characterization of a single cell’s morphology and molecular constituents (or at least a subset of the above) simultaneously. Similarly, combining electrode recording with optical methods provides added value. For example, including optical reporters like dyes or fluorescent proteins can help identify the recorded cell’s identity and connectivity.

All of neuroscience will benefit from a streamlined integration of optical technologies for large‐scale recording, optogenetic manipulation, and circuit reconstruction that allows multi‐faceted studies of identified cells and circuits in individual brains. This will encompass unified development of compatible optical hardware, genetic or chemical activity reporters, and optogenetic tools. Technology for optical studies of brain dynamics and circuitry, cell types, and molecular content should be progressively developed over the long‐term to attain sufficient throughput for sophisticated studies of the differences between individual subjects, in animals and in humans.

To reach their potential, optical methods should be viewed holistically. Wavelength ranges used for next‐generation multi‐color optical imaging and optogenetic control should ideally be tuned for mutual compatibility. Likewise, the capabilities and limitations of optical hardware should be taken into consideration when developing new sensor molecules, and vice versa, since the collective optical system is what ultimately should be optimized. For example, in the domain of optical sensors, much work is done at the surface of brain structures because imaging deep tissues remains a problem. Red or near infrared optical indicators would improve imaging depths in scattering tissues, but complementary strategies to solve this problem may be developed at the hardware‐sensor interface, for example via nonlinear optical excitation using long wavelength illumination.