Recent developments in optical microscopy techniques have revolutionized our ability to record, and more recently perturb, functional signals from identified elements in mammalian cortical circuits. We hope that, in the near future, we will be able to make use of these tools to not only uncover the basic operating principles of the cortical circuit – which underlie how we perceive, move and think – but also to aid in the development of therapeutic strategies for dysfunctioning cortical circuits – for instance following neurodegenerative disorders. In this talk, I will describe work in my laboratory on the development of enabling technology (both experimental and computational/theoretical) for reverse-engineering cortical circuit function, including two-photon targeted, robotically automated whole cell patch clamp electrophysiology, high fidelity action potential detection from calcium signals, novel galvanometric optical scanning algorithms, information theoretic data analysis methods, and novel decoding algorithms. I will illustrate the use of these tools with application to understanding the encoding of information underlying sensory perception, locomotion, and memory.