Nav: Home

New microscopy technique peers deep into the brain

April 15, 2019

In order to understand the brain, scientists must be able to see the brain--cell by cell, and moment by moment. However, because brains comprise billions of microscopic moving parts, faithfully recording their activity comes with many challenges. In dense mammalian brains, for example, it is difficult to track rapid cellular changes across multiple brain structures--particularly when those structures are located deep within the brain.

A novel microscopy technique, developed by Rockefeller scientists, integrates new and existing approaches to help build a more cohesive picture of the brain. Described in Cell, the technology captures cellular activity across large volumes of neural tissue, with impressive speed and at new depths.

Laser focused

For decades, brain imaging has been plagued by trade-offs. Some techniques produce beautiful images but fail to record neural activity in real time. Others can keep up with the brain's speed but have poor spatial resolution. And although there are tactics that successfully combine rapidity and image quality, they typically capture only a small number of cells.

"This is in part because the limits that govern these tradeoffs have not been explored or pushed in a systematic and integrated manner," says Alipasha Vaziri, head of the Laboratory of Neurotechnology and Biophysics.

Hoping to end the era of trade-offs, Vaziri recently endeavored to improve upon a technique known as two-photon (2p) microscopy. It involves the application of a laser that causes bits of brain tissue to fluoresce, or light up; and for many researchers, 2p has long been the gold standard for probing cellular activity in the brain.

Yet, this technique has limitations. Standard 2p microscopy requires point-by-point scanning of a given region, which results in slow imaging. To resolve this issue, Vaziri and his colleagues implemented a novel strategy that permits recording from multiple brain regions in parallel, while carefully controlling the size and shape of each spot recorded.

Another weakness of traditional 2p is that it measures only the surface, or cortex, of the brain, neglecting structures buried deep within the organ, such as the hippocampus, which is involved in storing memories.

"One of the biggest challenges in neuroscience is developing imaging techniques that measure the activity of deep brain regions while maintaining high resolution," says Vaziri.

Taking up this challenge, he decided to make use of a newer technology: three-photon (3p) microscopy. Whereas 2P doesn't reach beyond the surface, or cortex, of a mouse brain, 3p penetrates deeper regions. Called hybrid multiplexed sculpted light microscopy, or HyMS, Vaziri's latest innovation applies 2P and 3P concurrently, allowing researchers to generate a picture of rapid cellular activity across multiple layers of brain tissue.

Deep dive

In addition to its hybrid laser strategy, HyMS also integrates other recent technical and conceptual advancements in the field--a synergistic approach that, Vaziri says, guided the development of the technology. The goal, he says, was to maximize the amount of biological information that could be obtained through multi-photon excitation microscopy while minimizing the heat produced by this method. And when testing their new system, the scientists certainly obtained a lot of information.

HyMS boasts the highest frame rate of available 3p techniques, which means it can capture biological changes at record speed. And whereas previous techniques scanned only a single plane of tissue, this technology can obtain information from the entire tissue sample and allows users to record from as many as 12,000 neurons at once. Another advantage of HyMS is its ability to simultaneously measure activity from brain areas at different depths. Since different layers of the brain constantly exchange signals, says Vaziri, tracking the interplay between these regions is key to understanding how the organ functions.

"Before, people hadn't even been able to look at the activity of neurons over the entire depth of the cortex, which has multiple layers, all at the same time," he says. "With this technology you can actually see what the information flow looks like within the cortex, and between cortical and subcortical structures."

In addition to probing new depths, HyMS allows researchers to record brain activity from animals as they actively engage with their environment. In a recent experiment, for example, the researchers used the technology to record signals from thousands of mouse neurons as an animal walked on a treadmill or listened to sounds. The fact that they were able to obtain good recordings suggests that the technique may be used to monitor large cell populations as animals perform diverse tasks--an application that could help elucidate neural mechanisms underlying various aspects of behavior and cognition.

Further, says Vaziri, techniques like HyMS will be vital to researchers hoping to better understand how brains process information. Neurons in the brain are densely interconnected and information is often represented not by individual cells, but by states of the network.

"To understand the dynamics of a network," he says, "you need to get accurate measurements of big portions of the brain at a single-neuron level. That's what we've done here."
-end-


Rockefeller University

Related Neurons Articles:

Shaping the social networks of neurons
Identification of a protein complex that attracts or repels nerve cells during development.
With these neurons, extinguishing fear is its own reward
The same neurons responsible for encoding reward also form new memories to suppress fearful ones, according to new research by scientists at The Picower Institute for Learning and Memory at MIT.
How do we get so many different types of neurons in our brain?
SMU (Southern Methodist University) researchers have discovered another layer of complexity in gene expression, which could help explain how we're able to have so many billions of neurons in our brain.
These neurons affect how much you do, or don't, want to eat
University of Arizona researchers have identified a network of neurons that coordinate with other brain regions to influence eating behaviors.
Mood neurons mature during adolescence
Researchers have discovered a mysterious group of neurons in the amygdala -- a key center for emotional processing in the brain -- that stay in an immature, prenatal developmental state throughout childhood.
Astrocytes protect neurons from toxic buildup
Neurons off-load toxic by-products to astrocytes, which process and recycle them.
Connecting neurons in the brain
Leuven researchers uncover new mechanisms of brain development that determine when, where and how strongly distinct brain cells interconnect.
The salt-craving neurons
Pass the potato chips, please! New research discovers neural circuits that regulate craving and satiation for salty tastes.
When neurons are out of shape, antidepressants may not work
Selective serotonin reuptake inhibitors (SSRIs) are the most commonly prescribed medication for major depressive disorder (MDD), yet scientists still do not understand why the treatment does not work in nearly thirty percent of patients with MDD.
Losing neurons can sometimes not be that bad
Current thinking about Alzheimer's disease is that neuronal cell death in the brain is to blame for the cognitive havoc caused by the disease.
More Neurons News and Neurons Current Events

Trending Science News

Current Coronavirus (COVID-19) News

Top Science Podcasts

We have hand picked the top science podcasts of 2020.
Now Playing: TED Radio Hour

Uncharted
There's so much we've yet to explore–from outer space to the deep ocean to our own brains. This hour, Manoush goes on a journey through those uncharted places, led by TED Science Curator David Biello.
Now Playing: Science for the People

#556 The Power of Friendship
It's 2020 and times are tough. Maybe some of us are learning about social distancing the hard way. Maybe we just are all a little anxious. No matter what, we could probably use a friend. But what is a friend, exactly? And why do we need them so much? This week host Bethany Brookshire speaks with Lydia Denworth, author of the new book "Friendship: The Evolution, Biology, and Extraordinary Power of Life's Fundamental Bond". This episode is hosted by Bethany Brookshire, science writer from Science News.
Now Playing: Radiolab

Dispatch 2: Every Day is Ignaz Semmelweis Day
It began with a tweet: "EVERY DAY IS IGNAZ SEMMELWEIS DAY." Carl Zimmer – tweet author, acclaimed science writer and friend of the show – tells the story of a mysterious, deadly illness that struck 19th century Vienna, and the ill-fated hero who uncovered its cure ... and gave us our best weapon (so far) against the current global pandemic. This episode was reported and produced with help from Bethel Habte and Latif Nasser. Support Radiolab today at Radiolab.org/donate.