Rewriting Life
Time Travel Through the Brain
Over the last 100 years, the way we visualize and understand the complexity of the brain has evolved.
Visualizing Neurons
Nineteenth-century histologists created some of the first images of nerve cells by chemically stiffening tissue and then immersing it in silver nitrate, randomly staining a small number of cells to make them visible when they were viewed with powerful new light microscopes. The technique revealed the silhouette of the cell body and its network of extensions, and it enabled the great neuroanatomist Santiago Ramón y Cajal to prove that the nervous system consists of cells. He produced the 1899 drawing at left: it shows finely branched Purkinje cells, large neurons in the cerebellum that play an important role in controlling movement.
Developed in the 1930s, electron microscopes illuminate tissue samples with beams of electrons rather than light, increasing the maximum resolution so that much smaller structures can be distinguished. The image above, of a part of the brain stem that processes auditory information, shows a cluster of nerve-cell connections, magnified 23,900 times. The small, faint circles are synaptic vesicles, which ferry chemical signals between cells.
In the mid-1990s, researchers began marking specific cells in lab animals by genetically engineering the organisms to incorporate fluorescent proteins (above) found in marine species. Within 10 years, these proteins had been engineered into the cells in more complex ways, enabling researchers to monitor biochemical reactions and track the movements of cellular proteins in real time.
Confocal laser microscopy uses focused laser beams to scan tissue. The focused beam reduces the scattered light signal used in conventional microscopes, producing sharper, more detailed images. Light reflected back directly from each point is used to construct a three-dimensional image. This pyramidal neuron from the cortex of a mouse (above) was visualized by scanning the tissue at different depths and superimposing the series of images.
In the 1980s, scientists developed fluorescent dyes to help them examine the long, thin extensions of neurons that carry information between these cells. Injected directly into the brain, the dye is incorporated into the cell membrane and transported along it, revealing the route of the nerve fiber. This image highlights the long-range connections between sensory areas of a mouse’s cerebral cortex and thalamus, often called the brain’s relay station. Fibers from the primary visual cortex are shown in red, while fibers from the primary somatosensory cortex, which processes bodily sensations, are shown in green.
