Scientists on quest to map brain's wiring



There is a macabre brilliance to the machine in Jeff Lichtman’s laboratory at Harvard University that is worthy of a Wallace and Gromit film. In one end goes brain. Out the other comes sliced brain, courtesy of an automated arm that wields a diamond knife. The slivers of tissue drop on to a conveyor belt that zips along with the merry whirr of a cine projector.

Lichtman’s machine is an automated tape-collecting lathe ultramicrotome (Atlum). It produces long strips of sticky tape with brain slices attached, all ready to be photographed through a powerful electron microscope. When these pictures are combined into 3D images, they reveal the inner wiring of the organ, a tangled mass of nervous spaghetti. The research by Lichtman and his co-workers has a goal in mind that is unthinkably ambitious.

If we are ever to understand the brain in full, they say, we must know how every neuron inside is wired up.

Though fanciful, the payoff could be profound. Map out our ‘connectome’ - following other major ‘ome’ projects such as the genome and transcriptome - and we will lay bare the biological code of our personalities, memories, skills and susceptibilities. Somewhere in our brains is who we are.

To use an understatement heard often from scientists, the job at hand is not trivial. Lichtman’s machine slices brain tissue into exquisitely thin wafers. To turn a 1mm thick slice of brain into neural salami takes six days in a process that yields about 30,000 slices.

But chopping up the brain is the easy part. When Lichtman began this work several years ago, he calculated how long it might take to image every slice of a 1cm mouse brain. The answer was 7,000 years. The human brain is another story. There are 85bn neurons in the 1.4kg of flesh between our ears. Each has a cell body (grey matter) and long, thin extensions called dendrites and axons (white matter) that reach out and link to others.

Most neurons have lots of dendrites that receive information from other nerve cells, and one axon that branches on to other cells and sends information out. On average, each neuron forms 10,000 connections, through synapses with other nerve cells. Altogether, Lichtman estimates there are between 100tn and 1,000tn connections between neurons.

Unlike the lung, or the kidney, where the whole organ can be understood, more or less, by grasping the role of a handful of repeating physiological structures, the brain is made of thousands of specific types of brain cell that look and behave differently. Their names - Golgi, Betz, Renshaw, Purkinje - read like a roll call of the pioneers of neuroscience.