Why do we think like we do? How do the billions of neurons in your brain connect together to produce the myriad subtleties of human thought and emotion, let alone control and regulate your bodies? Questions such as these have been driving scientists ever since the brains role as master regulator was discovered.
Some progress has been made in answering these questions. Careful measuring of brain activity has allowed particular areas of the brain associated with specific tasks and functions. On a smaller scale, advances in microscopy and dissection techniques have revealed some of the astounding complexity of neuronal connections and synapses. However despite our best efforts, much of the brains mysteries remain.
Attempting to remove some of this mystery is the key focus of two current major international projects, the USA’s BRAIN initiative and the European Commission’s Human Brain Project. The BRAIN initiative’s goal is to completely map all connections within the human brain, while the Human Brain Project aims to build a computer that precisely mimics all we all know about the brain. These are vast projects with lofty ideas.
Projects such as these can only be successful if appropriate technologies and techniques exist to facilitate answering the questions posed. Thanks to the remarkable work of Karl Deisseroth and his team at Stanford University, one barrier to progress may have been removed.
Deisseroth has devised a method in which it is possible to turn human tissue, including brains, almost completely transparent. This method, aptly named CLARITY, is a great leap forward. It will allow researchers to quite literally peer into brains to examine how form and structure give the amazing functions of the brain we witness every day.
The technique is so important as it removes the current need to slice the brain into almost unimaginably thin slices before imaging can take place. This slicing means that recreating connections as they occur in the brain is tremendously challenging. CLARITY instead first uses a mixture of chemicals to ‘fix’ the proteins and structures of the brain in place. Then another chemical is added that removes light obscuring fats from within cells, replacing this with a clear, jelly-like substance.
Of course an entirely transparent brain would be relatively useless. To locate proteins and structures of interest the brain is exposed to chemical colour stains that bind specifically to proteins of interest. What’s more the brain can even be washed and re-stained to look for different things, something that was previously not possible
Already new features of the brain are being found. Deisseroth has a background in treating learning disorders, and so was quick to apply the technique to a deceased autism patient. He found ladder-like arrangements of neurons, not seen in ‘normal’ patients.
There is of course work to be done in fine tuning the technique, but taken alongside advances in microscopic imaging and computer modelling the potential for great science to be done is tantalising. A step forward in neuroscience has been made and it is clear for all to see.
Neuroscience: Solving the brain Nature 499, 272–274 (18 July 2013) doi:10.1038/499272a
Structural and molecular interrogation of intact biological systems, Chung et al., Nature 497, 332–337 (16 May 2013) doi:10.1038/nature12107