The ability to track the interactions of brain cells in animals in their natural habitat has been long sought after by neuroscientists and doctors. Researchers from The Rockefeller University have developed a system that is a huge step closer to this dream.

A mouse's hippocampal brain neurons flash on and off as the animal walks around with a microlens array on its head. Source: Laboratory of Neurotechnology and Biophysics at The Rockefeller UniversityA mouse's hippocampal brain neurons flash on and off as the animal walks around with a microlens array on its head. Source: Laboratory of Neurotechnology and Biophysics at The Rockefeller University

The new design is currently developed for use on mice, but the research team believes that one day it could be used to monitor neuronal activity in human beings. According to Alipasha Vaziri, leader of the development team and head of the Laboratory of Neurotechnology and Biophysics, this technology could lead to better understanding of the neuronal basis of many mental health issues, like autism.

As an animal moves around its environment, some neurons direct spatial navigation and other neurons receive sensory feedback from changes in body position or visuals.

"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 new tools can record the interplay among the neurons that are moving around and operating when two animals meet and interact socially.

The system has a tiny microscope that is attached to the mouse’s head and outfitted with a specialized group of lenses, called a microlens array. The microlens array allows the microscope to capture images from many angles and depths on the sensor chip. It produces a 3D record of neurons that are blinking on and off in communication with each other with electrochemical impulses. A coaxial cable is attached on the top of the microscope and this cable transmits data for recording. The gear weighs a total of four grams which is about as much as a mouse could possibly support. But the team is focusing on further developments to make the system way lighter.

After the sensor images have been gathered, the system has to process the raw data. Brain tissue is opaque, so it is difficult to pinpoint where the neuronal light flash is coming from. The team solved this problem by developing a new computer algorithm that fixes the issues and produces a clear image of individual neurons.

"The algorithm utilizes the statistical properties of neurons' distribution in space and in activity," Vaziri explained, "while extracting additional information from the scattered emission light. This enables their activity to be simultaneously and faithfully recorded within a volume despite of the highly scattering tissue properties."

This algorithm, called SID, has been used previously by Vaziri's lab in studies where the heads of the mice were secured in a fixed position. The latest research is the first of its kind to show all of these inventions that can be used together with the tiny microscope, called the Miniscope.

The technology could be huge for two-photon microscopy, which is a broadly used neuroscience tool. The new method captures data in 3D over the entire volume of tissue, which is faster and more effective.

"We hope this work will ultimately lead to a deeper understanding of how the brain processes information underlying the generation of behavior," said Vaziri.

The paper on our research was published in Nature Methods.