Stanford scientists have found a way of observing real-time brain activity in a live mouse, letting them work out where the mouse is in an enclosure on the basis of which neurons are firing.
The work could help develop new therapies for neurodegenerative diseases such as Alzheimer's.
The researchers first used gene therapy to make the mouse's neurons express a green fluorescent protein that was engineered to be sensitive to the presence of calcium ions. When a neuron fires, the cell naturally floods with calcium ions, stimulating the protein andcausing the entire cell to fluoresce bright green.
A tiny microscope implanted just above the mouse's hippocampus - critical for spatial and episodic memory - captures the light of roughly 700 neurons. The microscope is connected to a camera chip, which sends a digital version of the image to a computer screen.
The computer then displays near real-time video of the mouse's brain activity it runs around its enclosure - in which the scientists have deciphered clear patterns in the chao.
"We can literally figure out where the mouse is in the arena by looking at these lights," says associate professor of biology and of applied physics Mark Schnitzer.
When a mouse is scratching at the wall in a certain area of the arena, for example, a specific neuron will fire and flash green. When it moves to a different area, the light from the first neuron fades and a new cell sparks up.
"The hippocampus is very sensitive to where the animal is in its environment, and different cells respond to different parts of the arena," says Schnitzer. "Imagine walking around your office. Some of the neurons in your hippocampus light up when you're near your desk, and others fire when you're near your chair. This is how your brain makes a representative map of a space."
The group has found that a mouse's neurons fire in the same patterns, even when a month has passed between experiments. "The ability to come back and observe the same cells is very important for studying progressive brain diseases," Schnitzer said.
For example, if a particular neuron in a test mouse stops functioning, as a result of normal neuronal death or a neurodegenerative disease, researchers could try out a new therapy and then expose the mouse to the same stimuli to see if the neuron's function returns.