Neuroscientists Apply New 'Light Switch' Method to Decrypt Neuronal Microwiring

First Posted: Apr 10, 2013 03:14 PM EDT
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Applying a new method to decode the microwiring of the brain, Norwegian neuroscientists have used an optogenetic light switch to literally see which neurons communicate with each other in one small section of the brain.

The researchers at the Norwegian University of Science and Technology (NTNU)'s Kavli Institute of Systems Neuroscience used a virus that acts as a pathway for delivering "channelrhodopsin-2″ genes to specific "place cells" to create the equivalent of a light switch.

There are cells in the brain that do nothing else than recognize very specific places. While these "place cells" must be sent information from nearby cells to do their job, so far no one has been able to determine exactly what kind of cells work with place cells to craft the code they create for each location. Neurons come in many different types with specialized functions. Some respond to edges and borders, others to specific locations, others act like a compass and react to which way you turn your head.

Now, researchers at the Kavli Institute for Systems Neuroscience have developed a range of advanced techniques that enable them to identify which neurons communicate with each other at different times in the rat brain, and in doing so, create the animal's sense of direction.

"A rat's brain is the size of a grape. Inside there are about fifty million neurons that are connected together at a staggering 450 billion places (roughly)," explains Professor Edvard Moser, director of the Kavli Institute. "Inside this grape-sized brain are areas on each side that are smaller than a grape seed, where we know that memory and the sense of location reside. This is also where we find the neurons that respond to specific places, the place cells. But from which cells do these place cells get information?"

Neurons work by sending an electric current in one direction - from the "body" of the neuron down a long arm, called the axon, which goes to another nerve cell next in line. Place cells get their small electric signals from a whole series of such arms in this way.

The scientists used a special technique to make neurons sensitive to light to reveal the complex network between them. A special genetic recipe was used to enable a cell to make the equivalent of a light switch. A virus infection was used to introduce this recipe which converts neurons that have previously existed only in darkness, deep inside the brain, to now be sensitive to light.

"What we did first was to give these nerve arms a harmless viral infection," Moser says. "We designed a unique virus that does not cause disease, but that acts as a pathway for delivering genes to specific cells. The virus creeps into the neurons, crawls up against the electric current, and uses the nerve cell's own factory to make the genetic recipe that we gave to the virus to carry."

Then the researchers inserted optical fibers in the rat's brain to transmit light to the place cells. They also implanted thin microelectrodes down between the cells so they could detect the signals sent through the axons every time the light from the optical fiber was turned on.

The researchers then turned the lights on and off more than ten thousand times while they recorded the activity of hundreds of individual cells in the rats' grape-sized brains. The researchers did this research while the rats ran around in a meter-square box, gathering treats.

As the rats explored their box and found the treats, the researchers were able to use the light-sensitive cells to reveal how the rat's brain created the map of where the rat had been.

When the researchers put together all the information afterwards, they concluded that there is a whole range of different specialized cells that together provide place cells their information, such as grid cells, head-direction cells, and border cells. The brain's GPS - its sense of place - is created by signals from these different types of cells, they found.

They noted that while place cells receive information about the rat's surroundings and landmarks, they also continuously update their own movement, which is actually independent on sensory input.

Study:

Sheng-Jia Zhang et al., Optogenetic Dissection of Entorhinal-Hippocampal Functional Connectivity, Science, 2013, DOI: 10.1126/science.1232627

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