Chapter I
Ventricles and Tissue
For more than a thousand years, physicians following Galen placed the mind in the ventricles, the cavities in the middle of the brain filled with clear fluid. Perception, reason and memory were assigned to different ventricles in turn. The soft tissue around them was thought to be little more than padding.
In 1664 Thomas Willis, an Oxford physician, published the most careful account of the brain yet written, with plates drawn by his friend Christopher Wren. Willis argued from dissection and from his patients that the functions of the mind lie in the brain substance itself. He described the cerebral hemispheres, the cerebellum and the nerves leaving the brain with a new precision. The question now became which parts of the tissue do what.
Chapter II
Speech in the Left Hemisphere
The first convincing answer came from a patient. In 1861 Paul Broca, a Paris surgeon, examined a man who for twenty years had been able to say only one syllable, "tan". He understood speech and could answer with gestures. When the man died a few days later, Broca found a damaged patch in the left frontal lobe. More patients showed the same pattern, and by 1865 Broca concluded that speech is produced by the left hemisphere. In 1874 Carl Wernicke found that damage further back, in the temporal lobe, leaves speech fluent but destroys its understanding.
Experiment soon supported the clinic. In 1870 Gustav Fritsch and Eduard Hitzig passed weak electric currents through the cortex of dogs and made particular muscles twitch. The brain, it seemed, was a collection of organs, each with its job. What those organs were made of was still hidden, because under the microscope the grey matter looked like a dense tangle.
Chapter III
One Cell at a Time
In 1873 Camillo Golgi, working in a makeshift laboratory at a hospital for the chronically ill, found a way to cut through the tangle. Tissue hardened in potassium dichromate and soaked in silver nitrate showed a few nerve cells, apparently chosen at random, stained black from end to end. Because only a small fraction took the stain, each one stood out whole against a clear background, with its cell body, its branching dendrites and its long axon.
Golgi read his own images as showing that the fine fibres fused into one continuous net, the reticular theory held by most anatomists. Santiago Ramón y Cajal, a Spanish anatomist who learned of the stain in 1887, read them differently. By staining young birds and mammals, whose axons had not yet grown their fatty insulation, he could follow fibres to their ends, and they ended freely. Every nerve cell was a separate cell, as cell theory required of every other tissue. Heinrich Waldeyer named it the neuron in 1891. Cajal also argued, from the direction of branching, that signals flow one way, in through the dendrites and out along the axon.
Charles Sherrington, studying spinal reflexes in England, needed a name for the point where one neuron meets the next, and in 1897 he chose synapse. His experiments showed that synapses slow a signal, pass it only one way, and can inhibit as well as excite. In 1906 Golgi and Cajal shared the Nobel prize, and in Stockholm Golgi used his lecture to attack the neuron doctrine. The gap between neurons, about twenty nanometres, was too small for any light microscope. It was finally seen with the electron microscope of cell biology in the mid-1950s.
Meanwhile Korbinian Brodmann applied a different stain, which colours the bodies of all cells, to the whole cortex. In 1909 he divided it into areas numbered up to 52, by the thickness and cell types of its six layers. Borders drawn from cell structure alone often matched the borders of function that physiologists were finding.
Chapter IV
A Closer Look: Counting the Brain
How many neurons are there? Old textbooks said a hundred billion, with ten supporting glial cells for each, but nobody had counted. In 2009 Frederico Azevedo, Suzana Herculano-Houzel and colleagues dissolved whole human brains into a uniform soup of cell nuclei, counted samples, and stained the nuclei that belong to neurons. The averages for four adult men were:
| Region | Neurons (billions) | Share of neurons |
|---|---|---|
| Cerebral cortex | 16.3 | 18.9% |
| Cerebellum | 69.0 | 80.1% |
| Rest of the brain | 0.69 | 0.8% |
| Total | 86.1 | 100% |
The cerebral cortex, the seat of Broca's speech area and Brodmann's map, is about four fifths of the brain's mass but holds under a fifth of its neurons. The cerebellum, at the back, is about a tenth of the mass and holds four fifths of the neurons, most of them tiny granule cells. Glial cells turned out to be roughly as numerous as neurons, not ten times more.
Each neuron in the cortex makes thousands of synapses. Electron microscope counts put the number in the human neocortex at around , which is about
synapses for every cortical neuron.
All this runs on about 20 watts, the power of a dim light bulb. The brain is about 1.4 kg, 2% of a 70 kg body, but uses about 20% of the body's resting power of 100 watts. Per kilogram it burns energy ten times faster than the body as a whole. Shared among the neurons,
Splitting one molecule of ATP, the cell's energy currency from biochemistry, releases about 50 kJ per mole, or joules. So an average neuron consumes the equivalent of about 2.8 billion ATP molecules every second, most of it spent pumping ions back across its membrane after signalling. Over a day the brain uses about 1.7 million joules, some 410 kilocalories.
Chapter V
From Structure to Signal
By 1910 the brain had become a structure of parts: regions with jobs, built from separate neurons joined at synapses, each carrying signals one way. The anatomists could say where signals go but not what they are. The question of what travels along a nerve, and how fast, had been taken up by physiologists with galvanometers, and became electrophysiology. The map of regions, joined to recordings from single cells, later became systems neuroscience. Silver stains also revealed the plaques and tangles of Alzheimer's disease in 1906, and what causes that disease is still not agreed.