Live-imaging technique for mice seen as boost to studies of brain function and development

March 23, 2016
Using a specially customized wide-field microscope with dual lenses, University of Oregon researchers were able to put together a phase map showing regions of the mouse cortex that are active while encoding sensory stimuli. Colors indicate spatial positions (in azimuth) that elicit the largest responses. Credit: Joseph Wekselblatt

University of Oregon scientists have looked into the brains of living mice to see in real time the processing of sensory information and generation of behavioral responses.

To do so, researchers developed a line of transgenic mice whose brains expressed a green fluorescent protein that lights up active neurons. They then used a customized wide-field microscope with dual lenses to capture images of the brain similar to what fMRI does in humans. Combined, the technique allows them to visualize the activity across cortex, the outer surface of the brain.

"This is like fMRI but with far greater temporal and spatial resolution, " said Cristopher M. Niell, a professor in the Department of Biology and member of the UO's Institute of Neuroscience. "We can visualize sensory inputs as they come into the brain, and the subsequent activity corresponding to a decision and behavioral response. We see the whole flow."

The wide-field imaging approach developed for the research provides a new tool that can serve as a bridge connecting human fMRI to live imaging of mice to explore the underlying mechanisms and genetics of and development, said Niell and UO doctoral student Joseph B. Wekselblatt.

Live-imaging technique for mice seen as boost to studies of brain function and development
Technique combining customized wide-field microscopy and two-photon imaging allowed University of Oregon scientists to capture both the neural circuitry that is active across a mouse cortex and the specific neurons (shown as dots lighting up) involved from sensory input to a resulting behavior. Credit: Joseph Wekselblatt

They are two of the four UO co-authors on a paper, which is now in press with the Journal of Neurophysiology.

Large-scale brain imaging is currently possible in smaller species, such as zebrafish and nematodes, but they lack cortex—the top layer of mammalian brains where cognition, memory, language learning and motor behaviors occur.

The visualization is possible because of the fluorescent protein, GCaMP6, which was developed by researchers at the Howard Hughes Medical Institute. The protein contains a calcium sensor and lights up when neurons are activated. The mouse line with GCaMP6 generated at the UO is being distributed to scientists around the world through a repository at Jackson Laboratory in Maine.

The can be followed throughout their lives, enabling the study of changes in brain function over extended periods of time, such as throughout the learning of a task. It also opens the possibility, Niell said, to explore brain issues associated with early development, adolescent behavior, schizophrenia and age-related deterioration of the brain.

Human brain studies done with fMRI, a specially developed use of , allows researchers to pinpoint specific regions of the brain that are active under certain conditions by measuring changes in the level of blood oxygen. It does not allow researchers to probe deeper to see specific neuronal circuitry occurring as tasks are performed.

The final step of the new mouse-imaging system involves two-photon imaging, which allows researchers to zoom in and see that are active. Using the combination of wide-field and two-photon imaging, the researchers can study activity from the brain-wide global scale down to the local scale of groups of individual neurons.

"We deliver sensory inputs—moving images—that trigger decision-making by the mouse," Niell said. "As the inputs are registered and behavior begins, we can watch the flow of activity across the brain. You see it all in , and very quickly, nearly at the speed of thought."

"Our approach is faster than fMRI, where monitoring response is often measured in seconds," Wekselblatt said. "We see responses in a hundred milliseconds, and we can see the information flowing through cortex. You can't get that with fMRI. And then you can zoom in to see the circuitry behind the activation.

"In previous research, you'd have to use different animals at different times of their lives to get to information that you want," he said. "Here we can study the same mice over time to observe how patterns change when they are exposed to different variables, such as stress or medications."

By publishing their approach in the innovative methodology section of the Journal of Neurophysiology, the authors expect it will allow other researchers to use the approach in a wide range of studies of function, from sensory processing to cognition.

Explore further: Researchers track how brain routes visual signals

More information: Joseph B. Wekselblatt et al. Large-scale imaging of cortical dynamics during sensory perception and behavior, Journal of Neurophysiology (2016). DOI: 10.1152/jn.01056.2015

Related Stories

Researchers track how brain routes visual signals

March 11, 2016
Understanding how the brain manages to process the deluge of information about the outside world has been a daunting challenge. In a recent study in the journal Cell Reports, Yale's Michael Higley and Jessica Cardin from ...

Calcium waves in the brain alleviate depressive behavior in mice

March 22, 2016
Researchers at the RIKEN Brain Science Institute in Japan have discovered that the benefits of stimulating the brain with direct current come from its effects on astrocytes—not neurons—in the mouse brain. Published in ...

A new window into the brain

May 19, 2015
Tübingen neuroscientists have made an important advance in studying the human brain with functional magnetic resonance imaging (fMRI). This imaging technique is used in research endeavours to investigate the interactions ...

Study details brain pathways linking visual function, running

July 16, 2014
A new study by researchers at the University of Oregon published today in the journal Neuron describes a brainstem circuit in mice that may help explain how active movement impacts the way the brain processes sensory information.

Markov-inverse-F measure—a network connectivity approach using MVPA of fMRI

February 23, 2016
Multi-Voxel Pattern Analysis (MVPA) in functional magnetic resonance imaging (fMRI) studies is considered effective for studying how the human brain represents the meanings of words, when combined with a representational ...

Recommended for you

Scientists reveal new avenue for drug treatment in neuropathic pain

November 24, 2017
New research from King's College London has revealed a previously undiscovered mechanism of cellular communication, between neurons and immune cells, in neuropathic pain.

Small but distinct differences among species mark evolution of human brain

November 23, 2017
The most dramatic divergence between humans and other primates can be found in the brain, the primary organ that gives our species its identity.

Team constructs whole-brain map of electrical connections key to forming memories

November 22, 2017
A team of neuroscientists at the University of Pennsylvania has constructed the first whole-brain map of electrical connectivity in the brain based on data from nearly 300 neurosurgical patients with electrodes implanted ...

To forget or to remember? Memory depends on subtle brain signals, scientists find

November 22, 2017
The fragrance of hot pumpkin pie can bring back pleasant memories of holidays past, while the scent of an antiseptic hospital room may cause a shudder. The power of odors to activate memories both pleasing and aversive exists ...

Pitch imperfect? How the brain decodes pitch may improve cochlear implants

November 22, 2017
Picture yourself with a friend in a crowded restaurant. The din of other diners, the clattering of dishes, the muffled notes of background music, the voice of your friend, not to mention your own – all compete for your ...

New research suggests high-intensity exercise boosts memory

November 22, 2017
The health advantages of high-intensity exercise are widely known but new research from McMaster University points to another major benefit: better memory.

0 comments

Please sign in to add a comment. Registration is free, and takes less than a minute. Read more

Click here to reset your password.
Sign in to get notified via email when new comments are made.