Probing neural codes with two-photon holographic optogenetics

Multiphoton holographic optogenetics is opening the era of 'tailored' optogenetics. The authors review the underlying technology and discuss how it can be used to bridge the gap between experimental and theoretical neuroscience. Optogenetics ushered in a revolution in how neuroscientists interrogate brain function. Because of technical limitations, the majority of optogenetic studies have used low spatial resolution activation schemes that limit the types of perturbations that can be made. However, neural activity manipulations at finer spatial scales are likely to be important to more fully understand neural computation. Spatially precise multiphoton holographic optogenetics promises to address this challenge and opens up many new classes of experiments that were not previously possible. More specifically, by offering the ability to recreate extremely specific neural activity patterns in both space and time in functionally defined ensembles of neurons, multiphoton holographic optogenetics could allow neuroscientists to reveal fundamental aspects of the neural codes for sensation, cognition and behavior that have been beyond reach. This Review summarizes recent advances in multiphoton holographic optogenetics that substantially expand its capabilities, highlights outstanding technical challenges and provides an overview of the classes of experiments it can execute to test and validate key theoretical models of brain function. Multiphoton holographic optogenetics could substantially accelerate the pace of neuroscience discovery by helping to close the loop between experimental and theoretical neuroscience, leading to fundamental new insights into nervous system function and disorder.

Automated summary

Multiphoton holographic optogenetics is a tailored technique that can bridge the gap between experimental and theoretical neuroscience, offering spatial precision and the ability to create highly specific neural activity patterns to reveal fundamental aspects of neural coding for sensation, cognition and behavior. This technology has the potential to accelerate neuroscience discovery by helping to close the loop between experimental and theoretical neuroscience, leading to fundamental new insights into nervous system function and disorder.