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In an effort to really get inside the head of a rat, researchers at Bell Laboratories decided to stick a microscope inside an animal¿s skull. The results of their work, published in yesterday¿s Neuron, fell just short of their goal: observing brain cells in mobile rats.
Fritjof Helmchen and colleagues captured images of fluorescent dye traveling through blood vessels and brain cells in sleeping rodents, but the scientists could view only blood vessels in waking animals. To do so, they removed a small portion of the cranium and shined a laser light inside. In their microscope setup, a fiber-optic wire spat out photons as a piezoelectric crystal made it vibrate in two dimensions. A photomultiplier tube captured the light emitted from the dye, then a computer constructed an image by comparing the time the light entered the tube to where the fiber had been along its path at that time.
The images remained clear as the rats chewed and walked around but were obscured when the animals jerked their heads and, inevitably, banged the scope against their cages. An occasional brain twitch also tended to shift the image. Unfortunately, difficulties in getting the dye into brain cells and then finding them with the microscope prevented their visualization. The authors hope that by inserting DNA capable of producing a fluorescent protein into brain cells and by making the scope smaller and more maneuverable, they will overcome these difficulties. "[W]e have not quite succeeded in demonstrating what clearly is the ultimate goal of our efforts: functional imaging of neurons in freely moving animals," they write. "We still believe that [this] technology ... will eventually allow us to achieve this goal.
