The human brain is considered by many the most complex object in nature. Inside each of us is an organ chiseled from hundreds of millions of years of evolution, composed of billions of microscopic computational cells (neurons) that form dynamic, functional networks with one another to somehow give us our thoughts and senses. These ever-changing cognitive representations of sensory stimuli give rise to much of what makes us who we are: our memory, creativity, personality, the ability to read these words, and even to interpret my words in a (hopefully) meaningful way. In so many ways, researchers still don’t understand the precise ways in which the brain can accomplish these things, nonetheless explain how it can do so while consuming only 1/3 of the energy of a standard light bulb.
Brain cells fundamentally communicate with one another through rapid electrical signals, called action potentials. These brief blips of voltage result in the transfer of information from one cell to the next, while setting a host of complex intracellular chemical-signaling and gene-expression pathways into motion. Historically, scientists studying these events could only do by implanting sensitive microelectrodes into the brain, which are only able to sense signals from a single cell. However, recent advances in genetics and protein engineering have given rise to a new way to detect electrical activity in the brain: by seeing it.
Only during an action potential event, nearby charged ions dramatically rush into, or out of, the cell. One ion in particular, calcium, flows into the cell rapidly during an action potential, binding immediately to a calcium-sensitive intracellular protein called calmodulin. Remarkably, researchers have successfully modified the calmodulin protein without impairing its function, to include an additional domain which is able to fluoresce light only in the presence of calcium. By leveraging this calcium-calmodulin binding interaction which takes place during action potentials, one can use a standard optical fluorescent microscope to watch brain cells communicate.
To drive these proteins into cells of interest, scientists have gone a step further, by creating synthetic viruses that contain the exact genetic instruction set for making the fluorescent version of calmodulin (called GCaMP). When these viruses are injected into an organism, they integrate their genetic content with that of the cell itself, and by leveraging the mechanisms cells normally use to make calmodulin, produce GCaMP instead.
At this point, it is possible to watch neural circuits conduct computations in hundreds of cells as organisms learn, navigate, and recall memories. This genetic tool has been nothing short of transformative to the field of neuroscience, enabling a new discipline of in-vivo functional imaging which has already contributed key findings in our understanding of the brain.
