Small steps

They used a technique called expansion microscopy, which uses a substance called a hydrogel (the same material that makes diapers absorbent). Hydrogels absorb moisture by crosslinking with water molecules, swelling as they do so — a principle that researchers at the Boyden Lab at the Massachusetts Institute of Technology relied on to develop a tissue expansion protocol for microscopy in 2015.

Although expansion microscopy is used in many labs today, existing tissue expansion protocols do not preserve the tissue well enough to trace densely labeled neuronal structures, so our ISTA collaborators developed a new expansion protocol for LICONN. It involved first cutting a tiny block of tissue into 50 micrometer sections, then treating each section with a sequence of three different hydrogels. Two of the hydrogels created distinct, interweaving polymer networks within the tissue, with each one expanding the tissue by a factor of four, and the third hydrogel served to stabilize those networks. With this protocol, the tissue expanded by about 16 times in each direction, which is loosely comparable to starting with a sugar cube and ending up with a box of tissues.

The basic framework that I laid out for biology applies equally to neuroscience. The field is propelled forward by a small number of discoveries often related to tools for measurement or precise intervention – in the list of those above, optogenetics was a neuroscience discovery, and more recently CLARITY and expansion microscopy are advances in the same vein, in addition to many of the general cell biology methods directly carrying over to neuroscience. I think the rate of these advances will be similarly accelerated by AI and therefore that the framework of “100 years of progress in 5-10 years” applies to neuroscience in the same way it does to biology and for the same reasons.