New insight into how neural dynamics vary during spontaneous behavior

Previous studies have systematically linked spontaneous behaviors in mammals to variations in the activity of neurons in the cerebral cortex, the outer layer of the mammalian brain. However, the complex relationships between cortical activity patterns and behavior remain poorly understood.

Researchers at Yale University and the University of California, San Diego, recently conducted new experiments in mice aimed at exploring these connections further. Their article, published in Natural neuroscienceprovides new insights into how neurons in the mouse cortex represent behavioral information.

“Our laboratory has been developing approaches for several years to image activity in the cortex of awake, behaving mice,” Michael J. Higley, principal investigator of the team that carried out the study, told Medical Xpress. “These complex data sets present profound challenges for analyzing and interpreting their relationship with behavior. Through a collaboration with Ronald Coifman of the Yale Department of Mathematics, postdoctoral fellow Hadas Benisty used her expertise in mathematics and signal processing to look at our imaging data in new ways.”

The primary goal of the recent study by Higley and colleagues was to identify which aspects of neural signals associated with spontaneous behavior are most closely related to changes in the animal’s behavior in real time. To do this, they used optical imaging techniques that allow neuroscientists to closely examine the activity of specific cell types while the animals are awake and engaged in various activities.

“Normally, we divide the brain into several different areas and measure how activity increases and decreases over time in each region,” Higley said. “Previous studies (including those from our own lab) have looked at how these up-and-down fluctuations occur during measured changes in the animal’s behavior (like running on a wheel). Here, we also looked at how the correlations between “pairs” of zones vary over time.”

Higley and his colleagues found that these correlations in neuronal activity between cortical areas, often known as functional connectivity, tend to vary rapidly over time. This means that, for example, the similarity between activity in one area and another can be high and then become low within a few hundred milliseconds.

“We also observed, for the first time, that these rapid changes in correlations were also strongly coupled to rapid variation in the animal’s behavior,” Higley said. “Individual brain cells (neurons) are most strongly activated when receiving synchronized (correlated) inputs from many different regions. Thus, the temporal variation in these correlations suggests a distinct way in which individual cells might be modulated by The behaviour.”

The recent study by Highly and colleagues offers a new way to understand how neuronal dynamics vary depending on the animals’ spontaneous behavior. Specifically, this suggests that individual cells might be activated more when the inputs they receive are correlated with each other, and not simply when those inputs are strong.

In their next studies, the researchers plan to continue exploring the complex links between functional connectivity patterns and spontaneous animal behavior. First, they plan to try to identify causal links between neuronal activity and behavior using advanced research methods, such as optogenetic techniques.

“Using optogenetics, we can briefly disrupt activity or correlations in targeted areas and explore whether this manipulation changes the animal’s behavior,” Higley added.

“We would also like to extend our analyzes to more complex behaviors, such as mice actively navigating an environment in search of reward. Finally, we study the relationship between structured activity and behavior in genetic models of disorders neurodevelopmental disorders such as autism, to try to understand how a genetic disruption could ultimately lead to behavioral disruptions.

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