Jeff Lichtman and Joshua Sanes, researchers at the Harvard Brain Center, have created transgenic mice with fluorescent multicolored neurons. The photographs of the mouse brains that appear in the November 1, 2007 issue of Nature could be housed in the Museum of Modern Art or could be used to decorate Joseph's technicolored dream coat. But it is not their colorful splendor that makes these genetically modified mice so amazing. It is their potential to revolutionize neurobiology that excites scientists like myself and has our neurons firing away creating oodles of endorphins. Using a brainbow of colors researchers will now be able to map the neural circuits of the brain. The individually colored neurons will help define the complex tangle of neurons that comprise the brain and nervous system. By creating a wiring diagram of the brain researchers hope to help identify the defective wiring found in neurodegenerative diseases such as Altzheimer's and Parkinson's disease. In the Brainbow mice, the Harvard researchers have introduced genetic machinery that randomly mixes green, cyan and yellow fluorescent proteins in individual neurons thereby creating a palette of ninety distinctive hues and colors. "The technique drives the cell to switch on fluorescent protein genes in neurons more or less at random," says Jean Livet, the postdoctoral researcher responsible for most of the laboratory work that resulted in the Brainbow mice. "You can think of Brainbow almost like a slot machine in its generation of random outcomes."
FIG 1: cerebral cortex.
Service. R., Science NOW Daily News, 8 Ott 2008, 20
It's hard to believe but in non-living preserved brains the outerlayers of this portion of the brain are gray, which is why the brain is sometimes called "gray matter".
Mice are nocturnal animals that have made amazing adaptations to life in the dark. They have very sensitive whiskers (vibrissae) and an excellent sense of smell. To humans carbon dioxide is an odorless gas, but mice have special CO2 receptor molecules in their noses that can detect an increase in carbon dioxide. Perhaps they have developed this ability to detect the respiration of an approaching predator. Minmin Luo at the National Institute of Biological Sciences in Beijing trained mice to lick water whenever they detected an increase in CO2 levels.
The atmosphere typically contains 0.03% carbon dioxide, mice can detect CO2 concentrations of more than 0.06% CO2 in the atmosphere. In complementary work Peter Mombaerts at Rockefeller University has created a strain of mice in which the guanylyl cyclase-D expressing neurons are labeled with GFP. His research has shown that these olfactory neurons are activated by exposure to carbon dioxide.
Fine hair-like projections emanate from knobs at the tops of two GC-D expressing neurons. New research in mice has shown that GC-D expressing neurons in the olfactory epithelium are activated by exposure to carbon dioxide.
Anticancer Inc.have developed a nude transgenic mouse, see pictures below:
FIG 2: Mouse under blue light
When a blue light is shone on the mouse every cell (that contains actin) in its body will fluoresce green. Human cancers that express DsRed can be implanted into these mice. The cancers will give off red fluorescence. Now the cancer cells can easily be observed and monitored in live green mice. Allowing the researchers at Anticancer Inc. to observe metastasis (cancer cells moving around the body) and angiogenesis (blood vessels growing into the cancer and supplying oxygen and food).
Watching Mice Think
Karel Svoboda at the Cold Spring Harbor Laboratories on Long Island is doing something no one else has ever done before. He is watching how mice think. He doesnt sit and watch a mouse in a maze with a puzzled expression on its face no, he watches the brain of a mouse react to new experiences. Joshua Sanes, a collaborator of his from the Washington University School of Medicine in St. Louis, created a transgenic mouse strain that expresses GFP in some of the neurons in the cortex. Then together with some of his students and collaborators, Svoboda has replaced sections of the skulls of these transgenic young mice with transparent windows, so that they can watch what happens to the region of their cortices, which processes sensory information derived from their whiskers. The mice can live out their entire lives with the windows in place, allowing Svoboda the opportunity to monitor the changes occurring over many weeks. He observed tiny spines along the dendrites rising and receding. The rate of spine turnover increased as the mice were exposed to new experiences. The figure belowe shows YFP and GFP labeled cerebral neurons in two lines of transgenically modified mice. Karel is now continuing his work at the HHMI Janelia Farm.
FIG 3: Fluorescent protein expression in the cerebral neurons in two different lines of transgenic mice. In the one line, GFP is expressed sparsely; in the other YFP is expressed abundantly. Both pictures were taken through a glass window embedded in live mice.