Imaging the engram in mice

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In a human brain, 85 billion nerve cells communicate via trillions of connections using complex patterns of electrical jolts and more than 100 different chemicals. One way to understand how this complex system works is to "watch" it while it performs its normal functions. That is, one way to understand how the brain encodes and stores information is to examine neural function in real time while an animal performs a memory task.***In the 1890s, the pioneering neuroscientist, Santiago Ramón y Cajal, microscopically examined human brain cells and wrote of massively interconnecting webs of tightly packed cells, which he described as "impenetrable jungles where many investigators have lost themselves". Since that time, however, there have been numerous advances in microscopy which now allow researchers to examine rodent brain function "at the speed of thought". ***Previously neuronal activity has been assessed using in vivo electrophysiological techniques in which electrodes or wires were implanted into the brain and activity of handfuls of neurons recorded while an animal is behaving some sort of task. Although this technique offered many important insights into how brain activity correlates with behaviour, it was difficult to determine exactly which neuron was firing. The next innovation allowed researchers to literally see into the brain and monitor neuronal firing by using rodents expressing genetically-encoded calcium indicators (which fluoresce upon neural activation) and using 2-photon microscopy. This approach can be well-suited for examining the activity of neurons on the surface of the brain, but requires that the animal be restrained (head-fixed to an immovable microscope), which likely also stresses the animal. In contrast, the proposed mini-microscope, which is small enough to be mounted on the head of a mouse will make it possible to "watch" brain cell activity and while the mouse freely-behaves. This mini-microscope, though, will enable chronic recording of neural activity while an animal is performing some sort of task (memory test, social interaction, or other behaviour) without inducing stress. *** ***We believe that this visionary technology will enable researchers to stimulate one brain region and record the neural consequences in several other brain regions at the same time. This will allow us to understand not only how small portions of neurons within a brain region function, but how the brain functions overall. This technology will allow us to create a dynamic map of the brain which is crucial to understanding brain function.**