May 14, 2018
Like many Neurophysiologists, Professor Tony Zador of Cold Spring Harbour Laboratory found himself frustrated with our limited ability to accurately map neuron projections in the brain. Although traditional fluorescence microscopy has advanced the field significantly, it is limited in how few neurons can be tagged simultaneously, its resolution and the ability to image large areas of tissue with high resolution.
Imagine then, the excitement around Professor Zador’s recent Nature publication in which he was able to create a 3D rendering of 50 000 neurons in a mouse cortex with single-cell resolution. His lab’s new technique, Multiplexed Analysis of Projections by Sequencing (MAPseq) was demonstrated to have high accuracy with large numbers of neurons.
The idea for MAPseq was conceived when Professor Zador took into account the fast growth and increasing affordability of high-throughput genomic sequencing. MAPseq essentially acts as a bridge between this and brain mapping.
In this publication, mice were injected with viruses genetically modified to carry known RNA sequences. After an incubation period, each neuron in the mouse’s cortex would be tagged with a specific RNA sequence – referred to here as a “bar code”. The brain is then sectioned, and each section is run through a DNA sequencer. The results of this allow for the accurate construction of a 3D model of neurons and their projections in the mouse cortex.
According to Professor Zador, this technique is also much more affordable than traditional mapping techniques. Mapping 100 000 neurons in under two weeks with MAPseq would only cost approximately 75 000 GBP.
This technique is an exciting addition to the repertoire available to neuroscientists and has already been used in research on pathways in the visual system to great effect. It must, however, be noted that MAPseq is not the one key to unravelling the mysteries of the brain. It can not provide information on function or location of calls being tagged, nor can it show which cells are communicating with which. MAPseq would simply provide researchers with a map, allowing researchers to better understand the terrain they seek.