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  3. Prefrontal cortex reaches back into the brain to shape how other regions function
December 19, 2025

Prefrontal cortex reaches back into the brain to shape how other regions function

by
David Orenstein | The Picower Institute for Learning and Memory
Image
Prefrontal cortex reaches back into the brain to shape how other regions function
An image from new MIT research shows where neurons from the ACA (red) and ORB (green) regions of the prefrontal cortex innervate the visual cortex.

Vision shapes behavior and, a new study by MIT neuroscientists finds, behavior and internal states shape vision. The new research, published Nov. 25 in Neuron, finds in mice that via specific circuits, the brain’s executive control center, the prefrontal cortex, sends tailored messages to regions governing vision and motion to ensure that their work is shaped by contexts such as the mouse’s level of arousal and whether they are on the move.

“That’s the major conclusion of this paper: There are targeted projections for targeted impact,” says senior author Mriganka Sur, the Paul and Lilah Newton Professor in The Picower Institute for Learning and Memory and MIT’s Department of Brain and Cognitive Sciences.

Neuroscientists, including Sur’s next-door office neighbor at MIT, Earl K. Miller, have long suggested that the prefrontal cortex (PFC) biases the work of regions further back in the cortex. Tracing of anatomical circuits supports this idea. But in the new study, lead author and Sur Lab postdoc Sofie Ährlund-Richter sought to determine whether the PFC is broadcasting a generic signal or customizes the information it conveys for different downstream regions. She also wanted to take a fresh look at which neurons the PFC talks to, and what impact the information has on how those regions function.

Ährlund-Richter and Sur’s team uncovered several new revelations. One was that the two prefrontal areas they focused on, the orbitofrontal cortex (ORB) and the anterior cingulate area (ACA), selectively convey information about arousal and motion to the two downstream regions they studied, the primary visual cortex (VISp) and the primary motor cortex (MOp), to achieve distinct ends. For instance, the more aroused a mouse was, the more ACA prompted VISp to sharpen the focus of visual information it represented, but ORB only chimed in if arousal was very high, and then its input seemed to reduce the sharpness of visual encoding. Ährlund-Richter speculates that as arousal increases, ACA may help the visual cortex focus on resolving what might be salient in what it’s seeing, while ORB might be suppressing focus on unimportant distractors.

“These two PFC subregions are kind of balancing each other,” Ährlund-Richter says. “While one will enhance stimuli that might be more uncertain or more difficult to detect, the other one kind of dampens strong stimuli that might be irrelevant.”

In the study, Ährlund-Richter performed detailed anatomical tracings of the circuits that ACA and ORB forge with VISp and MOp to map their connections. In other experiments, mice were free to run on a wheel as they also watched both structured images or naturalistic movies at varying levels of contrast. Sometimes the mice received little air puffs that made them more aroused. Meanwhile, the neuroscientists tracked the activity of neurons in ACA, ORB, VISp, and MOp. In particular, they eavesdropped on the information flowing through the neural projections (or “axons”) that extended from the prefrontal to the posterior regions.

The anatomical tracings showed that complementary with some prior studies, the ACA and ORB each connect to many different types of cells in the target regions, not just one cell type. But they do so with distinct geographies. In VISp, for instance, ACA tapped in to layer 6, whereas ORB tapped into layer 5.

In their analysis of the transmitted information and neural activity, the scientists could discern several trends. ACA neurons conveyed more visual information than the ORB neurons and were more sensitive to changes in contrast. ACA neurons also scaled with arousal state, while ORB neurons seemed to only care if arousal crossed a high threshold. Meanwhile, when “talking” to MOp, the ACA and ORB each conveyed information about running speed, but with VISp, the regions only conveyed whether the mouse was moving or not. Finally, ACA and ORB also conveyed arousal state and a trickle of visual information to MOp.

To understand what effect this information flow had on visual function, the scientists sometimes blocked the circuits that ACA and ORB forged with VISp to see how that changed what VISp neurons did. That’s how they found that ACA and ORB affected visual encoding in specific and opposite ways, based on the mouse’s arousal level and movement.

“Our data support a model of PFC feedback that is specialized at both the level of PFC subregions and their targets, enabling each region to selectively shape target-specific cortical activity rather than modulating it globally,” the authors wrote in Neuron.

In addition to Sur and Ährlund-Richter, the paper’s other authors are Yuma Osako, Kyle R. Jenks, Emma Odom, Haoyang Huang, and Don B. Arnold.

Funding for the study came from a Wenner-Gren foundations Postdoctoral Fellowship, the National Institutes of Health, and the Freedom Together Foundation.

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