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Today, scientists can safely examine these connections in a living human brain using a variation of magnetic resonance imaging (MRI) called diffusion tensor imaging. This technique, developed in the 1990s, infers the location of nerve fibers by tracking water molecules in the brain as they move along them. The image above shows fibers radiating from the thalamus in a human brain.
Credit: Thomas Schultz/University of Chicago
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.
Credit: Maria Carmen Piñon and Zoltán Molnár/University of Oxford
The Third Dimension
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.
Credit: Tony Pham, Baylor College of Medicine
In the 1990s, scientists developed a way to further reduce the scatter of light, called two-photon microscopy. This approach, which uses infrared light, can probe deeper into live tissue, producing images like the section of mouse cerebellum shown above.
Credit: Alanna Watt and Michael Häusser, UCL
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.
Credit: Koki Moriyoshi et al., Neuron, February 1996
Scientists can now label nerve cells in a rainbow of colors. This image is of a “Brainbow” mouse, which has been engineered so that different nerve cells glow in dozens of hues; it shows the hippocampus, a brain area that is crucial for memory. This technology, developed in 2007, has revealed the connections between cells in remarkable detail.
Credit: Jean Livet, INSERM