Abstract:

For decades, scientists and physicians have electrically recorded and stimulated neurons deep in the brain with implanted electrodes: The former is known as electrophysiology while the latter represents a major therapy – deep brain stimulation – that is widely used to treat patients with neurological symptoms. However, these electrical approaches lack cell specificity and are largely invasive. The past decade has witnessed the emergence of optical methods to precisely image and modulate the activities of genetically defined neurons in vivo. In this lecture, I will introduce two cutting-edge optical approaches, optogenetics and in vivo imaging, in neuroscience research. In particular I will highlight how chemistry plays an essential role in generating actuators and sensors for these neurotechnologies.

Optogenetics harnesses genetically encoded light-gated ion channels, the so-called rhodopsins, to optically stimulate target neurons. Variants of rhodopsins with various kinetic and spectral parameters have been developed to activate or inhibit neurons. I will present an example to illustrate how optogenetics is used to interrogate neural circuits for learning and memory. Although optogenetics has revolutionized experimental neuroscience, for deep brain applications it has a limitation that it requires the insertion of invasive optical fibers. I will discuss our recent work to employ upconversion nanoparticles to shift the optogenetic spectra to the near-infrared region that enables transcranial near-infrared brain stimulation.

While optogenetics is used for neural modulation, in vivo optical imaging is well applied for recording neuronal activities. Calcium and voltage indicators have been developed to probe neuronal activity, nanoparticles have been used for tracking molecular transport in neurons, while two-photon microscopy has enabled deep tissue imaging at a high resolution. These technical advances have allowed real-time functional imaging of neurons in behaving animals, contributing to the understanding of cognitive processes in the brain such as how memory is encoded.

Further development of optical approaches for brain science will require cross-disciplinary collaborations involving chemists who develop molecular sensors and actuators. These achievements will rapidly pave the way not only to a better understanding of how the brain works but also towards a bright therapeutic future for patients with brain diseases.

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