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This lecture explores the use of light- and calcium-gated tools to investigate neuronal activity, focusing on optogenetics. The presentation covers the principles of optogenetics, genetically-encoded tools for probing neuronal activity, and the potential applications in neuroscience and beyond. It delves into the development of optogenetic devices, their mechanisms, and their role in studying brain information processing. Additionally, it discusses the clinical trials involving optogenetic restoration of vision in conditions like Retinitis Pigmentosa. The lecture also touches on neurotransmission basics, neuronal structures, and genetically-encoded tools' specificity, speed, sensitivity, dynamic range, and photostability. It concludes with a look at directed evolution methods to engineer light-responsive fusion proteins for controlled neuronal activity.