Home Cellular science New research to understand how the brain works

New research to understand how the brain works

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image: Xana Waughman, a neuroscientist at the Allen Institute, describes recordings of mouse neuron activity – in a technique known as 2-photon microscopy, scientists are able to capture neurons firing and turn off thanks to a fluorescent sensor designed to light up with cellular activity. This technique is one of those used in OpenScope, a shared brain observatory program at the Allen Institute.
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Credit: Allen Institute / Erik Dinnel

By Rachel TompaPhD / Allen Institute

What happens in our brain when we are tricked by an optical illusion? How do our neurons take shortcuts to avoid sensory overload while absorbing the world around us? What happens when our predictions of the world don’t match reality?

New research projects are underway at the Allen Institute to answer these questions through OpenScope, the shared neuroscience observatory that allows scientists around the world to propose and lead experiments conducted on one of the experimental platforms at broadband of the Institute.

OpenScope was launched in 2018opening the Allen Brain Observatory to researchers outside the Institute. The Allen Brain Observatory is a standardized experimental platform that allows scientists to study the mouse brain in action. Currently, scientists are studying the visual regions of the mouse brain as the animals see and react to different images or movies; the Observatory team plans to expand to other brain regions in the coming years.

Last year, OpenScope received a 5-year grant from the National Institute of Neurological Disorders and Stroke to support its work, in which experts at the Allen Institute conduct experiments proposed by researchers outside the institution. Institute and transmit the resulting data to these researchers for analysis. Data from OpenScope projects, like all data from the Allen Brain Observatory, is also made public for anyone in the scientific community to use.

Seventeen teams of researchers from around the world applied to lead OpenScope projects, and a scientific committee selected three projects to run on the platform this year. The projects are led by researchers at Vanderbilt University; the University of California, Berkeley; and York University and McGill University in Canada.

The “shared observatory” approach is inspired by astronomical observatories, such as the Mauna Kea Observatories in Hawaii or the Kitt Peak National Observatory in Arizona, where astronomers from around the world can sign up for time on powerful equipment too expensive for individual organizations. Using OpenScope, scientists can access the Allen Institute’s equipment as well as experimental expertise, through the lab’s researchers who do the hands-on work.

In the age of neuroscientific big data, the techniques for collecting this data are becoming more sophisticated, more complicated and more expensive. A community platform like OpenScope can help democratize some aspects of this kind of science, providing access to researchers who may not have the funds or time to conduct such large-scale experiments in-house. said Jerome LecoqPh.D., research associate at the Allen Institute, who directs the OpenScope program.

“It’s a more inclusive process,” Lecoq said.

“We hope to demonstrate that this shared platform can be a new model for generating data in neuroscience. It is increasingly difficult to collect these types of datasets, so we believe that more community observatories will be needed, to complement the existing in-house research model.

What illusions can teach us about the brain

All of this year’s OpenScope projects address how the mouse brain perceives the visual world – and more specifically, how the brain’s representation of the world differs from reality in different and important ways. A project, led by neuroscientists at UC Berkeley Hyeyoung Shindoctorate and Hillel AdesnikPh.D., aims to discover how the neurons of the visual system react to optical illusions.

“A lot of sensory neuroscience focuses on how accurately the brain can represent information. But in the process, we kind of forget that perception isn’t meant to be an accurate representation of sensory information. On the contrary , it’s meant to be an interpretation,” Shin said. “The illusions really bring out the dichotomy between what we’re expecting and what the sensory information is giving us.”

In this project, OpenScope scientists will show mice images of different optical illusions (yes, mice are fooled by optical illusions just like us) and measure the activity of neurons that respond to using a device called Neuropixels – tiny silicon probes capable of recording the activity of hundreds or thousands of neurons in a single experiment. Shin and Adesnik previously used a different method in their own lab to study how mouse neurons respond to optical illusions. The neuropixels will allow them to test a theory from their previous work: neurons responding to the sight of a single object – or what the brain thinks is a single object, in the case of the illusion – fire up in synchrony .

How neurons integrate unexpected signals

Another OpenScope project seeks to understand how the brain processes unexpected visual information, by examining different neural signals that meet in a single neuron. Normally, the visual parts of the brain combine expectations (based on past experiences) with actual sensory information (light hitting the retinas) to build a representation of the world around us. These two different signals meet and fuse in individual brain cells, each signal reaching one end of long small neurons whose branching processes span several layers of the visual part of the mammalian brain.

York University Neuroscientist Joel ZylberbergPh.D., and neuroscientist at McGill University Blake Richards, Ph.D., are leading a project to understand what happens to these merging signals when visual information doesn’t match what the brain expects. The Allen Institute scientists will show the mice a movie while recording the activity of their neurons, and then at some point, like Twin Peaks, the movie will start playing in reverse.

“We want to see at the cellular level, what’s happening in the brain when this mismatch occurs,” Richards said.

Richards and Zylberberg, who both also led one of the first OpenScope projects, are computational neuroscientists. They spend a lot of time coming up with theories about how the brain works, Zylberberg said.

With OpenScope, “instead of publishing a theory and waiting to see if other scientists will do a related experiment, we can now take the theory, design and deliver the experiment ourselves, and collaborate with the Allen Institute , then do the analysis,” says Zylberberg.

“I think it speeds up the scientific process considerably.”

How to Avoid Sensory Overload

Your brain is a big consumer of energy. The human brain uses about 20% of the body’s energy, more or less. The mouse brain is not as greedy, in proportion to its size, but the activity of neurons in general is calorie intensive. So the brain looks for shortcuts wherever it can.

The third OpenScope project explores a general theory around the conservation of brain energy known as predictive coding, which states that the brain saves a lot of its activity to react to the unexpected. When everything in our environment is as expected, the brain stops paying attention. This not only helps us save energy, the theory goes, but it also helps us focus on potentially dangerous or potentially rewarding new situations that might arise from the unexpected. A specific type of neuron that inhibits the activity of other neurons may be involved in the “subtraction” of what is already expected.

Imagine walking into a familiar room in your home and everything is as you left it. Your brain won’t have much to do in this situation. But if you walk into your living room and there’s a red box sitting on the coffee table that wasn’t there a few minutes ago, your attention will shift to that new and unexpected object.

Vanderbilt University scientists Alex Mayerdoctorate, Andre Bastosdoctorate and Jacob Westerberg lead a project to explore the neuroscience of predictive coding, also using Neuropixels to measure neuron activity. OpenScope researchers will record the activity of thousands of neurons in several connected brain areas when mice are exposed to expected or unexpected images. These animals are genetically engineered to mark certain types of neurons, allowing researchers to know which types of inhibitory neurons are active during experiments.

“For me, this model seems to be the future. The data collection side can really only be done by the Allen Institute. I can’t think of any other place where it could be done,” Maier said. “Opening up this resource to investigators like us who don’t have it available, and then dividing the work in terms of who collects the data and who analyzes the data, seems like a quantum leap to me.”

The research described in this article was supported by award number U24NS113646 from the National Institute of Neurological Disorders and Stroke of the National Institutes of Health. The contents are the sole responsibility of the authors and do not necessarily represent the official views of the NIH and its subsidiary institutes.