Researchers at the Rockefeller University have developed a tiny headset that can visualize neurons in the brain turning on and off while a mouse explores its environment, or interacts with other mice. The technique could help scientists to track the interactions between brain cells and learn more about what happens in the brains of people with disorders such as schizophrenia.
Tracking brain activity in the lab is a challenge, as many imaging techniques require an animal to stay still during imaging, meaning that it isn’t behaving naturally. In addition, it is difficult to identify which neurons play a role in navigation or social activity, as this requires an animal to be able to move freely and act naturally.
The Rockefeller research group has developed a new approach that allows them to see inside the brain, while an animal is moving freely. Their device includes a tiny microscope, which they call a Miniscope, that is mounted on the head of a mouse. The microscope is attached to a microlens array that allows the researchers to image the brain at different depths and angles. The headset weighs only four grams, but the research team has plans for further miniaturization in the future.
The mice in question are genetically modified so that their neurons light up when they are activated. However, as the brain is opaque, the research team employed an algorithm that allowed them to analyze the raw data and pinpoint where in the brain each neuronal ‘flash’ came from.
“The algorithm utilizes the statistical properties of neurons’ distribution in space and in activity, while extracting additional information from the scattered emission light,” said Alipasha Vaziri, a researcher involved in the study. “This enables their activity to be simultaneously and faithfully recorded within a volume despite of the highly scattering tissue properties.”
The resulting images show neurons flashing on and off in sequence. The device can immediately capture 3D images, and does not require a later 3D reconstruction step, such as that needed with some other imaging techniques.
This approach has many applications. To date, the researchers have investigated the neurons involved in navigating an environment. “Until now, no one has been able to detect how these different neurons, which can be located at different depths within a volume of brain tissue, dynamically interact with each other in a freely moving rodent,” said Vaziri.
The group hopes that their technique could eventually help them understand the neuronal basis for behavior, and allow them to track brain activity in certain disorders.
Study in Nature Methods: High-speed volumetric imaging of neuronal activity in freely moving rodents…
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