Lighting up the brain

Delicate ascension

Neuroscientist Andreas Zembrzycki uses dyes and fluorescent genes to light up neurons in the brains of young mice. The technique allows him to track how sensory nerves form and connect in the mammalian brain.

In the above image, Zembrzycki, who is from the Salk Institute for Biological Studies in California, traced the connections of two sensory neurons located in the visual cortex and somatosensory cortex of the brain (the star-shaped structures, bottom right). The one in the visual cortex (dyed red) receives signals from the eyes, and one in the somatosensory cortex (dyed green) receives touch sensations from the skin. “When you sit at the microscope and you see it, you are stunned – always,” he says.

Wires intertwined

The neocortex, where all our senses come together, is the most recently evolved part of the brain. Sight, sound and touch signals directed through the thalamus – the switchboard of the brain – meet and communicate in the neocortex to conjure a picture of the outside world.

Imagine you’re chasing a soccer ball. Tracking the moving ball with your eyes, feeling the ground through your feet, your brain can swing your leg with split second timing to launch the ball towards goal. But you also need to adapt quickly – say a strong wind starts blowing or a teammate yells a command.

“Information is constantly fed into the brain, integrated and filtered in the neocortex to execute decisions and movements. These higher order sensory areas are heavily interconnected,” says Zembrzycki.

In the above image you can see this close-knit relationship. Neurons transmitting touch and pain (green) and vision (red) are closely intertwined and talk to each other as signals fire between them.

Transitions

We all start from one fertilised cell that keeps on dividing. Each newborn cell migrates precisely, sometimes over long distances, to reach their final destination.

As an embryo develops, neurons of the cortex form from stem cells that line hollow fluid-filled spaces in the brain called ventricles. This microscope image above shows the growing brain of a 12-day-old mouse embryo genetically engineered to light up different cell types. Daughter cells, generated from stem cells (red), migrate to the outer layers of the cortex to become mature neurons (green).

A change of fate

How does a newly born neuron decide whether to dedicate itself to touch, sight or sound?

Above is a microscopic snapshot of the two hemispheres of a 12-day-old embryonic mouse brain, with budding stem cells in blue and mature neurons in green. Scientists had thought that neurons were programmed to work in a particular sensory area as they bud from stem cells. But Zembrzycki has shown that young neurons – marked here in bright red and yellow – are still capable of change even after completing their migration to the outer cortex.

Zembrzycki and his colleagues found that by switching off a gene called Lhx2 large regions of the cortex that would normally process touch and sound reprogrammed themselves to process vision. The work was published in Proceedings of the National Academy of Sciences in April.

Lhx2 is a master switch that affects many other genes, including some that are influenced by our environment such as stress or diet. This research indicates that our environment early in life could have more influence on our brain than scientists previously imagined.

“We know that for years after birth, neurons in a child’s brain are still being wired up,” Zembrzycki says. People with autism spectrum disorder can be overly sensitive to light, touch or sound, and an imbalance of those sensory neurons may be partly to blame. Knowing which genes and environmental factors affect those neurons might one day help treat the condition.