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
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
A newer twist on electron microscopy, developed in the 1980s, can reveal the internal structures of nerve cells. Researchers use a detergent to remove the cell membrane. Platinum and carbon are deposited onto the exposed surfaces to reproduce the cell’s interior features as a three-dimensional mold, which is then examined in the microscope. This image shows a hippocampal neuron that has been stripped of its membrane to expose the cytoskeleton, a scaffold that regulates the cell’s growth and movement.
Credit: Bernd Knöll (University of Tübingen), Jürgen Berger, and Heinz Schwarz (Max-Planck-Institute for Developmental Biology)
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.
Credit: Palay, 1956. Originally published in the Journal of Biophysical and Biochemical Cytology, 2: 193-202
Fluorescent dyes can now be injected directly into cells to stain the ones a researcher wants to view. This image shows a Purkinje cell in red and a nerve fiber from another cell in green. A single Purkinje cell is connected to hundreds of thousands of these fibers.
Credit: Michael Häusser, University College London