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A stop-motion movie of the whole brain, starring new neurons

by  /  21 October 2019
A new technique helps reveal patterns in the migration of neurons (green) to their destination (red).
Cells on the move: A new technique helps reveal patterns in the migration of neurons (green) to their destination (red).

A new method visualizes nascent neurons in the mouse brain and follows them as they migrate to their final destinations.

The method — essentially a time series of 3D images — may shed light on processes that unfold during brain development.

“We take snapshots at different time points, then match them together to see dynamic processes,” says Alexander Lazutkin, senior scientist at the P.K. Anokhin Institute of Normal Physiology in Moscow, Russia. Lazutkin presented the work yesterday at the 2019 Society for Neuroscience annual meeting in Chicago, Illinois.

Researchers can use the method to study the birth of neurons and the complex ways in which they migrate through the brain. Abnormalities in these processes have been implicated in autism.

In the weeks after a mouse is born, neural stem cells in its brain continue to divide and generate neurons. Lazutkin’s team marked these dividing cells throughout the brain by adapting a fluorescent labeling technique typically used on thin sections of tissue. (The labeling method was published 12 September in MethodsX1.)

In the new work, they labeled cells in the brains of adult mice. They used a fluorescent microscope to take a snapshot of the whole brain of one set of animals, and then a different set of animals one day older the next day, and so on. They built an algorithm to stitch the images together and fill in the gaps to form a time series.

The result is a movie that tracks cells’ locations as they migrate toward their destination. The cells originate in the subventricular zone, one of two places where cells continue to divide in the adult brain. The movie shows the migrating cells reaching the olfactory bulb in about 10 days.

It also shows cells forming a stripe pattern in the subventricular zone.

“We suppose these are distinct migration streams,” Lazutkin says. “You can’t see this pattern on a conventional [2D] slide. But when you have the full picture, you can recognize them.”

Lazutkin and his colleagues plan to use the method to look at differences in early brain development between typical mice and mouse models of autism — particularly those with mutations that lead to altered brain growth.

For more reports from the 2019 Society for Neuroscience annual meeting, please click here.


References:
  1. Lazutkin A.A. et al. MethodsX 6, 1986-1991 (2019) Full text