Rockefeller University » New microscopy technology answers fundamental questions

Light bead microscopy has made it possible to increase the number of neurons that can be recorded simultaneously by a factor of 100.

The mammalian brain is a densely interconnected web of neurons, but one of the mysteries in neuroscience is how scientists can use tools to capture relatively small components of brain activity in mice. The question is whether it has become possible to predict the behavior of people. It's hard to believe that much of the brain's complexity is extraneous background noise. “We wondered why such a redundant and metabolically expensive scheme had evolved,” Rockefeller said. Minister Alipasha.

now, new research in neuronThis study, an unprecedented simultaneous recording of the activity of one million neurons in mice, provides a surprising answer to this fundamental question. Technological limitations are misleading us, and there is much more to the brain than we once thought.

“Previous assumptions about the true dimensions of brain dynamics may have been due to a lack of ability to record from a sufficiently large number of neurons,” Vaziri says.

Using custom techniques developed in the Basili lab, the researchers demonstrated the independent dimensions needed to describe the observed neuronal dynamics, including the observed dimensions of neural activity (signals distinct from noise). We found that over 90 percent of the elements) were: It is not related to the spontaneous movements or sensory inputs of the mice studied. Thousands of these dimensions, containing more than half of the mouse's cumulative neural activity, span the entire brain spatiotemporally, ranging from minutes to seconds in time, without forming distinct clusters in any region. It has spread to

The mice were clearly using this widespread and continuous activity for some purpose. But for what? “We don't know yet, but it's definitely a signal that is different from noise,” Vaziri said. “This could provide a doorway to a variety of complex internal states and neural computations.”

neural flash

Vasili's lab focuses on developing optical techniques that advance neuroscience and enable observation of the simultaneous activity of many neurons distributed throughout the brain. In 2021, the laboratory will optical bead microscopy, a two-photon imaging technology that uniquely enables a 100-fold increase in the number of neurons that can be recorded simultaneously. To test this technology, the researchers recorded for the first time the activity of more than 1 million neurons across the mouse brain's cortex, allowing the animals to capture spontaneous, undirected behaviors from different angles with multiple cameras. Observed. Things like running on a treadmill and grooming.

Because of the demonstrated effectiveness of this tool, the lab became interested in using it to address fundamental questions in neurobiology. “We had tools that allowed us to make discoveries that other technologies couldn't make,” says Baziri. “So we tried to ask a question that only such a tool could answer: How much more information is being extracted as we continue to record from more and more neurons? What does that information represent?”

To investigate, researchers used LBM in combination with advanced data analysis, computational modeling, and machine learning techniques to study neural activity as mice move spontaneously and respond to their environment. .

the missing 90 percent

Neural activity related to animal movement is known to be streamlined into low-dimensional subspaces, and previous techniques that can record fewer neurons have made it possible to identify these connections. “However, it is thanks to the capabilities of LBM that we were able to discover that more than 90 percent of the remaining dimensions contain reliable signals that are distinct from noise and that are not required for behavior and are not explained by environmental stimuli. ” Vaziri says.

Unexpectedly, these neurons were also firing everywhere. “What are they doing? We don't know,” Vaziri says. “They may underlie a brain-wide network of correlated neural fluctuations, perhaps related to the dynamics of some internal state, such as hunger or motivation.”

How this applies to the human brain remains to be seen (“Compared to a pond in a mouse brain, the human brain is an ocean,” Vaziri says), but the new study's findings , strongly suggests that we are only beginning to understand the true complexity of the human brain. mammalian brain.

A new type of observatory

LBM is Rockefeller Brain ObservatoryThis is a new effort led by Vaziri to give neuroscientists access to pioneering equipment not available commercially that “can do things that would otherwise be impossible,” Vaziri said. To tell.

The facility resembles an observatory and allows visiting scientists to conduct research with powerful instruments. “The idea is that the staff will support you as you conduct your research using the center’s microscopes,” he says. “We want to make this available not only to the internal Rockefeller community, but also to neuroscientists around the world.”

Vaziri and his team are also helping researchers at several universities, including Stanford University and UCL London, reproduce the LBM technique in their own neuroscience labs. The data they collect from the current study will also be available for analysis by other researchers.

They also want to expand the scope of LBM. “We would like to welcome research groups working with different model systems other than mice, for example insects or primates. We therefore need a more versatile, robust and user-friendly version of his LBM. ,” Vaziri said. Say.