A New Way to Watch Brain Activity in Action

It's a neuroscientist's dream: being able to track the millions of interactions among brain cells in animals that move about freely, behaving as they would under natural circumstances. New technology developed at The Rockefeller University represents a big step toward realizing that goal.

The invention, reported today in Nature Methods, is expected to give researchers a dynamic tool to study the brain's role in various behaviors. Although it is designed for use on mice, information gleaned from it could someday shed light on neuronal activity in humans as well, says Alipasha Vaziri, who led the technology's development as head of the Laboratory of Neurotechnology and Biophysics. For example, it might allow us to better understand the neuronal basis of brain disorders such as autism and schizophrenia.

Vaziri says the tool provides an opening to an exciting range of discoveries. As an animal moves about its environment, for instance, some neurons direct spatial navigation while others receive sensory feedback from changes to the body's position or the visual system. "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," says Vaziri, an associate professor at Rockefeller. Similarly, the tool can be used to record the interplay among neurons when two animals meet and interact socially.

High-tech headgear

The technology consists of a tiny microscope attached to a mouse's head and outfitted with a specialized group of lenses called a microlens array. These lenses enable the microscope to capture images from multiple angles and depths on a sensor chip, producing a three-dimensional record of neurons blinking on and off as they communicate with each other through electrochemical impulses. (In the experiments, the mouse neurons are genetically modified to light up when they become activated.) A coaxial cable attached to the top of the microscope transmits the data for recording. The head-mounted gear weighs about four grams, about as much as a mouse can support, but Vaziri expects that planned modifications will make it significantly lighter.

Once the microlens array has captured sensor images from within a volume of brain tissue, the next challenge is to process this raw data. Brain tissue is opaque, making it difficult to pinpoint the source of each neuronal light flash. Vaziri's team solved this problem, which is the result of so-called scattering, by developing a new computer algorithm. "The algorithm utilizes the statistical properties of neurons' distribution in space and in activity," Vaziri explains, "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."

The result is a clear image that shows individual neurons flashing in sequence.

Faster, more effective imaging

Vaziri's lab has previously applied this algorithm, known by the acronym SID, in studies in which the heads of the mice were secured in a fixed position. Their latest research is the first to demonstrate that these inventions can be used together with a tiny microscope called the Miniscope, developed by a collaborating team at the University of California Los Angeles, to measure neuronal activity volumetrically in unconstrained animals.

The technology, if widely adopted, could offer several advantages over two-photon microscopy, a broadly used neuroscience tool. For example, two-photon microscopy records neuronal activity within individual focal planes - thin, virtual "slices" of the sample - that then are combined to create a three-dimensional image. In contrast, Vaziri's method immediately captures data in three dimensions over an entire volume of tissue, making it faster and more effective.

Vaziri plans to continue developing tools to record neuronal activity in even larger portions of the brain than is currently possible, and at higher speeds and resolution. "We hope this work will ultimately lead to a deeper understanding of how the brain processes information underlying the generation of behavior," he says.

Oliver Skocek, Tobias Nöbauer, Lukas Weilguny, Francisca Martínez Traub, Chuying Naomi Xia, Maxim I Molodtsov, Abhinav Grama, Masahito Yamagata, Daniel Aharoni, David D Cox, Peyman Golshani, Alipasha Vaziri.
High-speed volumetric imaging of neuronal activity in freely moving rodents.
Nature Methods (2018). doi: 10.1038/s41592-018-0008-0.

Most Popular Now

Merck and Tencent Announce Collaboration…

Merck, a leading science and technology company, signed a strategic collaboration agreement with Tencent, a leading provider of Internet value added services. The collaboration will primarily focus on increasing public...

Merck Granted U.S. Patent for Novel Comb…

Merck, a leading science and technology company, today announced that it has been granted Patent No. US 10,193,695 by the United States Patent and Trademark Office (USPTO). The patent relates...

Applications Now Open for Pioneering Dig…

The Yorkshire & Humber AHSN (Academic Health Science Network), in partnership with mHabitat, announces that applications for the 2019 Propel@YH digital health accelerator programme are now open. Propel@YH has been...

The European Health Catapult Program for…

Through dedicated sessions, a group of international top-level investors, key healthcare leaders and industry stakeholders work closely together challenging 40+ ambitious startups to optimize their business plan and strengthen their...

Flagship Axe the Fax Trust Rolls out Hyb…

Leeds Teaching Hospitals NHS Trust (LTHT), the organisation at the forefront of the national Axe the Fax campaign, is implementing an electronic fax solution to tackle its last remaining machines...

First EU Citizens Using ePrescriptions i…

The first EU patients can use digital prescriptions issued by their home doctor when visiting a pharmacy in another EU country: Finnish patients are now able to go to a...

Final Report: Provision of a Market Stud…

The aim of the study is to examine the telemedicine market in Europe and to understand the factors that determine its development. The analysis maps telemedicine applications and solutions, and...

Open Access Drug Development Tools Featu…

New open access tools for drug development, obesity, and the environmental impacts of medicines are the focus of a new IMI2 Call for proposals launched today. The total budget of...

Boehringer Ingelheim (Canada) Ltd. and I…

Boehringer Ingelheim (Canada) Ltd. and IBM Canada announced at the Healthcare Information and Management Systems Society (HIMSS) conference in Orlando, Florida, their plans to explore the use of blockchain technology...

The NHS Long Term Plan: Cracking the Da …

Opinion Article by Prof. Michael Thick, Chief Medical Officer, Chief Clinical Information Officer, IMS MAXIMS Reading the NHS Long Term Plan this week, I had a definite sense of déjà vu...

Highland Marketing Advisory Board Respon…

The first meeting of Highland Marketing's newly expanded advisory board discussed the NHS Long Term Plan and what will be needed to make it a success. Structural change, leadership, investment...