Developed by researchers at the Boston University School of Medicine and Harvard University, the imaging method employs an automated tape-collecting device equipped with a diamond knife to obtain ultra-thin brain sections, which are then scanned under an electron microscope. Different colors are used to identify different cellular objects using software developed by study co-author Daniel Berger.
To demonstrate their new tool the researchers peered inside the brain of an adult mouse. They imaged a very small piece of a mouse's neocortex at a resolution that made individual synaptic vesicles visible (these are tiny spheres of less than 40 nm diameter that store neurotransmitters, or chemical signals, for release from a synapse into a "target" neuron). The specific area they imaged is involved in receiving sensory information from mouse whiskers, which are much more sensitive than human fingertips.
It had previously been thought that the connectivity between axons and dendrites could be inferred from their locations – a concept called Peters' Rule, despite the fact that the man responsible for the idea disputes it. The researchers proved this is not the case. There is a more complex relationship between axons and dendrites, which causes multiple synapses to form on some dendrites but not on others. The best predictor of synapse formation turns out to be the presence of another synapse between that same axon and dendrite pair.
Further, study first author Narayanan "Bobby" Kasthuri says that the complexity of the brain is far greater than anyone had imagined. "We had this clean idea of how there's a really nice order to how neurons connect with each other," he explains, "but if you actually look at the material it's not like that. The connections are so messy that it's hard to imagine a plan to it. But we checked, and there's clearly a pattern that cannot be explained by randomness."
Nanoscale imaging of the brain means that in every square micrometer of tissue we can see things we've never seen before. It promises huge opportunities for discovery and exploration, and it promises that someday, in the far flung future, we may have our answers – we may learn everything there is to learn about how the brain works.
Many scientists see the work as a waste of time and money, senior author Jeff Lichtman notes – it is simply too enormous an undertaking to yield much value. But surely we as a species must continue to dream big, to chase the impossible, because history has taught us that the journey, the striving for more answers, proves as rewarding and fruitful as the goal that we may never reach.
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