Harvard Medicine

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Going Viral

TRAFFIC PATTERN: An enlargement of a region of a mouse brain shows the transit of green-hued virus as it travels along neurons and moves across synapses. </br>Photo: Michelle Ocana/Neurobiology Imaging Facility, HMS Neurobiology DepartmentGlowing in the darkness like an island seen from on high, a slice of the brain of a mouse shows blue neurons hugging its coastline and green neurons traversing the interior. This is a sliver of the cerebellum, the part of the brain where motor control resides. It is an image with quiet beauty, but it is also an image that tells a story about the connections neurons make—a story that may have surprising implications for human health.

Scientists in the Department of Neurobiology at HMS are mapping the landscape between neurons to gain a deeper understanding of brain function. They are tracking how neurons communicate with one another by following the trail of chemical or electrical signals these cells send across specialized structures called synapses.

CLOSE SHAVE: Three sections of a mouse brain showing the movement of a green-tagged virus.</br>Photo: Michelle Ocana/Neurobiology Imaging Facility, HMS Neurobiology DepartmentNew technologies in neuroimaging are making it easier to see neurons and neural paths. Some of the neurons in this mouse cerebellum, for example, were infected with a virus engineered to produce a green fluorescent protein. Once this virus entered the neuron, it replicated and traveled along the neuron and dendrites to the synapses, where it jumped to connecting neurons. Other neurons were stained with blue dye, allowing the researchers to see the brain’s different structures, thus providing a sort of cellular topography against which to reference the movements of the fluorescing virus. The researchers then used a fluorescent microscope to find the traveling viruses and to observe the dispersal of green to pinpoint synaptic connections and see how information flows through the brain.

The investigators expected the synaptic connections infected with the engineered virus to be localized in the areas of the brain involved in motor control, but instead they found the virus had traveled to connections beyond the cerebellum. The virus had spread to parts of the brain associated with higher-level cognitive function.

The scientists next plan to train a different type of light on these extracerebellar connections through a technique called optogenetics. They will again infect the neurons with a virus, this one producing a protein called channelrhodopsin. This photoresponsive protein will allow the researchers to use light as a switch to control synaptic activity in live animals.

“We hope to see how we influence a mouse’s behavior when we activate synaptic connections,” says Skyler Jackman, a research fellow in the laboratory of Wade Regehr, an HMS professor of neurobiology.

What they learn could be far-reaching.

“This could help us gain insight into how cerebellar dysfunction in humans might lead to neuropsychiatric disorders,” Jackman says.