Abstract:

Chemical biology approaches that allow for in vivo recording and modulation of neuronal activities hold the key to understanding how the brain works and developing next-generation therapies for neurological diseases. Despite significant technical progress in synthetic chemistry over the past decades, the application of synthetic molecules and materials to reading and controlling cognition in the living brain is still in its infancy. In this talk, I will first introduce the synthesis of a voltage-responsive molecular machine to illustrate how the state-of-the-art of synthetic chemistry has allowed us to create molecular systems whose energy conversion and logic flow can be precisely controlled. I will then show how molecularly tailored artificial actuators, in particular upconversion nanoparticles, can be used for non-invasive optical stimulation of specific neurons nestled deep in the brain. This technology, called NIR upconversion optogenetics, has allowed for transcranial modulation of various brain functions, such as evoking dopamine release, inducing brain oscillations, and triggering memory recall. Finally, I will share an example to demonstrate the power of chemical biology approaches, in particular optogenetics and tissue-clearing technologies, in making fundamental neuroscience discoveries when combined with physiological and behavioral experiments. Tagging and manipulation of defined neurons have allowed us to identify a previously unknown novelty hub in the mammalian brain that plays an essential role in memory modulation. Collectively, these works shed light on a new avenue of chemical biology that aims at cutting-edge applications in neuroscience, ranging from probing how the brain works at molecular and systems levels to modulating brain activities for potential neurological therapies.

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