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A pioneering detailed map of mouse cerebral activity has been revealed by an extensive global partnership of neuroscientists.
Investigators from the International Brain Laboratory (IBL), including MIT neuroscientist Ila Fiete, released their publicly accessible results today in two papers in Nature, providing revelations into how decision-making transpires across the complete brain in mice at a single-cell level. This comprehensive activity map of the brain contests the conventional hierarchical perspective of information management in the brain and illustrates that decision-making is distributed across numerous areas in a remarkably coordinated manner.
“This is the inaugural instance of anyone crafting a full, brain-wide map of the activity of individual neurons during decision-making,” clarifies IBL co-founder Alexandre Pouget. “The scale is unparalleled as we recorded from over half-a-million neurons across mice in 12 laboratories, encompassing 279 brain regions, which collectively represent 95 percent of the mouse brain volume. The decision-making activity, particularly regarding rewards, illuminated the brain like a festive light display,” adds Pouget, who is also a group leader at the University of Geneva in Switzerland.
Modeling decision-making
The cerebral map was made viable by a significant international collaboration of neuroscientists from various universities, including MIT. Researchers across 12 laboratories employed advanced silicon electrodes, known as neuropixels probes, for simultaneous neuron recordings to measure brain activity while mice engaged in a decision-making task.
“Joining the International Brain Laboratory has provided fresh avenues for our group to contribute to scientific knowledge,” states Fiete, who is additionally a professor of brain and cognitive sciences, an associate investigator at the McGovern Institute for Brain Research, and director of the K. Lisa Yang ICoN Center at MIT. “Our lab has assisted in standardizing methods for analyzing data and generating robust conclusions. As computational neuroscientists keen on developing models of brain function, the access to brain-wide recordings is remarkable: the classic method of recording from one or a few brain regions limited our capacity to construct and evaluate theories, resulting in disjointed models. Now, we encounter the delightful yet daunting task of understanding how all segments of the brain collaborate to perform a behavior. Surprisingly, having a complete overview of the brain leads to simplifications in decision-making models,” explains Fiete.
The laboratories gathered data from mice performing a decision-making task involving sensory, motor, and cognitive aspects. In this task, a mouse is positioned in front of a screen, where a light appears on either the left or right side. If the mouse then reacts by turning a small wheel in the accurate direction, it earns a reward.
In certain trials, the light is dim enough that the animal must guess which way to move the wheel, utilizing prior knowledge: the light tends to appear more often on one side over several trials before switching to the high-frequency side. Well-trained mice learn to leverage this information to aid them in making accurate guesses. These challenging trials thus allowed the researchers to examine how previous expectations affect perception and decision-making.
Brain-wide results
The first paper, “A brain-wide map of neural activity during complex behaviour,” demonstrated that decision-making signals are unexpectedly distributed throughout the brain, rather than confined to specific regions. This adds brain-wide evidence to an increasing number of research studies that question the traditional hierarchical model of brain function, underscoring that there is continuous communication among brain regions during decision-making, the onset of movement, and even reward. This suggests that neuroscientists will need to adopt a more comprehensive, brain-wide approach in the study of complex behaviors in the future.
“The unprecedented scope of our recordings unveils how the entire brain executes the full spectrum of sensory processing, cognitive decision-making, and movement generation,” asserts Fiete. “Establishing a collaboration that collects a large standardized dataset that individual labs could not compile is a groundbreaking new direction for systems neuroscience, ushering the field into a hyper-collaborative mode that has triggered advances in particle physics and human genetics. Beyond our own findings, the dataset and associated technologies, which were released much earlier as part of the IBL mission, have already evolved into a widely used resource for the entire neuroscience community.”
The second paper, “Brain-wide representations of prior information,” indicated that prior expectations — our beliefs regarding the probable outcomes based on recent experiences — are encoded throughout the brain. Interestingly, these expectations are evident not only in cognitive regions, but also in brain areas that process sensory information and control actions. For instance, expectations are even encoded in early sensory regions such as the thalamus, the brain’s initial relay for visual input from the eye. This supports the idea that the brain functions as a prediction machine, but with expectations encoded across multiple brain structures playing a vital role in guiding behavioral responses. These discoveries could offer insights into understanding conditions such as schizophrenia and autism, which are believed to stem from differences in how expectations are updated in the brain.
“Much remains to be unraveled: If it is feasible to detect a signal in a brain region, does it imply that this area is generating the signal, or merely reflecting a signal produced elsewhere? How significantly does our perception of the world get influenced by our expectations? Now we can obtain some quantitative answers and commence the next phase of experiments to explore the sources of the expectation signals by intervening to modulate their activity,” comments Fiete.
Looking forward, the team at IBL plans to broaden their initial focus on decision-making to investigate a wider array of neuroscience questions. With renewed financial support, IBL aims to expand its research agenda and continue facilitating large-scale, standardized experiments.
New model of collaborative neuroscience
Officially launched in 2017, IBL established a new mode of collaboration in neuroscience that utilizes a standardized set of tools and data processing routes shared amongst multiple laboratories, allowing for the collection of extensive datasets while ensuring data alignment and reproducibility. This strategy seeks to democratize and speed up scientific progress, drawing inspiration from large-scale collaborations in physics and biology, such as CERN and the Human Genome Project.
All data from these investigations, along with detailed specifications of the tools and protocols utilized for data collection, are openly available to the global scientific community for further analysis and research. Summaries of these resources can be accessed and downloaded on the IBL website under the sections: Data, Tools, Protocols.
This research was funded by grants from Wellcome, the Simons Foundation, the National Institutes of Health, the National Science Foundation, the Gatsby Charitable Foundation, as well as by the Max Planck Society and the Humboldt Foundation.
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