The transplanted cells formed circuits, reached the spinal cord and responded to injury.
In recent years, there has been a lot of excitement about the potential for studying human diseases in what are called "organoids." These small patches of tissue, formed using stem cells, appear to produce many of the same cell types and at least some of the structures normally formed in actual organs, and thus can provide a better model for diseases that rely on the sometimes complex interactions among multiple specialized cell types that are a feature of the human body.
But even the most sophisticated organoids lack a lot of the features of a real human body. This is especially true for brain organoids, which don't form any of the connections with specialized brain structures needed to behave "normally." On Wednesday, a research group at Stanford University described a possible way to study brain organoids in a somewhat more natural context: They genetically wiped out a large portion of the mouse brain and replaced it with human brain organoid cells.
Organoids, because they adopt a three-dimensional tissue structure and consist of various specialized cells, provide a much better model for an intact tissue than simply having a bunch of disassociated cells lying flat on a culture dish. But they still have a lot of limitations—they're not hooked up to a circulatory system that allows the liver to process chemicals the organoid produces and don't have immune cells moving through them, to give just a couple of examples.
© S. Pasca lab, Stanford University
In recent years, there has been a lot of excitement about the potential for studying human diseases in what are called "organoids." These small patches of tissue, formed using stem cells, appear to produce many of the same cell types and at least some of the structures normally formed in actual organs, and thus can provide a better model for diseases that rely on the sometimes complex interactions among multiple specialized cell types that are a feature of the human body.
But even the most sophisticated organoids lack a lot of the features of a real human body. This is especially true for brain organoids, which don't form any of the connections with specialized brain structures needed to behave "normally." On Wednesday, a research group at Stanford University described a possible way to study brain organoids in a somewhat more natural context: They genetically wiped out a large portion of the mouse brain and replaced it with human brain organoid cells.
Organoids, because they adopt a three-dimensional tissue structure and consist of various specialized cells, provide a much better model for an intact tissue than simply having a bunch of disassociated cells lying flat on a culture dish. But they still have a lot of limitations—they're not hooked up to a circulatory system that allows the liver to process chemicals the organoid produces and don't have immune cells moving through them, to give just a couple of examples.
© S. Pasca lab, Stanford University
The human brain is remarkably adept at juggling different kinds of information, allowing us to switch rapidly between tasks and adapt our behavior as circumstances change. A new study by MIT neuroscientists takes a closer look at how the brain accomplishes this, providing evidence for flexible neural modules that may help support this cognitive versatility.
Using mice, scientists found that a group of neurons in the prefrontal cortex could switch between retaining sensory information and maintaining an action plan in working memory.
“We found that the brain doesn’t dedicate a separate group of neurons for every type of information,” says Yuma Osako, an MIT postdoc and the lead author of the new study. “Instead, it uses the same populations of neurons to perform the same computation on different kinds of information, which means the same subset of neurons can hold both an action and a sensory stimulus in working memory,”
The findings also lend support to a longstanding theory known as compositionality—the idea that cognition can be constructed by combining and reusing neural components.
“One of the solutions that’s always been proposed has been this idea of compositionality — that you can take pieces of cognition that perform part of a task and reuse them in another task,” says Timothy Buschman, a professor at the Princeton Neuroscience Institute, and the senior author of the paper, in a statement.
Another way to see this is to view it as “cognitive Legos,” Buschman suggests. Instead of building a new neural circuit when a new task starts, the brain reuses existing circuits and combines them in different ways.
To see how this neural network operates, the scientists trained mice to compare two tones and respond depending on whether the sounds matched. As the mice performed the tasks, the scientists recorded electrical activity from thousands of neurons.
“When mice do tasks that test whether memory computations can be reused, the answer is they are,” notes Mriganka Sur, the Newton Professor of Neuroscience at MIT’s Picower Institute for Learning and Memory. “There are subspaces of functional activity in the prefrontal cortex that can be the substrate of mixing and matching toward flexible cognition.”
Two important components of the task allowed the researchers to examine how different kinds of information were maintained. First, the mice had to remember the initial tone for a short period. They then had to retain their decision and form an action plan.
In the parietal cortex, neurons were dedicated to storing information about the tone. However, researchers found something different in the prefrontal cortex: a specific group of neurons could switch roles.
During one stage of the task, the circuit helped maintain a sensory memory. During another, the same population was involved in maintaining an action plan. This flexibility may help explain how a finite number of neurons can support an enormous range of behaviors.
“Our everyday life requires us to temporarily hold many different kinds of information. One big question is how the brain can represent an unlimited variability of information using only a finite number of neurons,” Osako says.
The researchers view these reusable neural circuits as potential building blocks for flexible cognition. More broadly, the findings suggest that the brain may be less like a machine filled with components dedicated to individual tasks and more like an interconnected system that continually repurposes its existing neural resources.
The recent study appeared in the journal Nature.
Chrissy Newton is a PR professional and the founder of VOCAB Communications. She currently appears on The Discovery Channel and Max and hosts the Rebelliously Curious podcast, which can be found on YouTube and on all audio podcast streaming platforms. Follow her on X: @ChrissyNewton, Instagram: @BeingChrissyNewton, and chrissynewton.com. To contact Chrissy with a story, please email chrissy @ thedebrief.org.
Scientists have uncovered new details about how the brain’s “information hub” responds to uncertainty, revealing a remarkably flexible system that rapidly changes how it communicates with other brain regions as we make decisions.
Every second of our lives, the human brain sorts through enormous amounts of information. From remembering a driving route and handling daily tasks to making decisions, the brain must continually determine what information matters and how to respond. Researchers at the University of Iowa wanted to better understand how the human brain manages and processes this information and found that it may be more flexible than previously thought.
At the center of this sorting process is an area of the brain known as the frontoparietal cortex. This region supports decision-making and behavioral control and can function as a kind of “information hub” for the brain.
Using MRI scans, behavioral experiments, and computational modeling, researchers took a deeper look at how the frontoparietal cortex responds when people are uncertain about what they should do next.
“That’s the main contribution,” says Kai Hwang, associate professor in the Department of Psychological and Brain Sciences and the study’s corresponding author, in a statement.
“Our study shows in more detail how the frontoparietal cortex operates — what kind of information it extracts from other systems and how it uses its connectivity pattern to integrate information that is coming in from different areas of the brain,” Hwang adds.
The research team recruited 38 participants between the ages of 18 and 35 and had each person learn associations between combinations of colors, faces, and scenes and particular actions—for example, pressing a button with the index or middle finger of either hand. The researchers then intentionally changed those associations.
When an action or rule changes, the brain has to determine what went wrong.
Did the situation change? Was the information unclear? Or did the person simply make a mistake? This uncertainty allowed researchers to observe how the brain’s “information hub” responds under different circumstances.
“It’s like where other areas of the brain don’t have all the information, so they send what they have to the frontoparietal cortex for guidance,” Hwang explains.
The results from the team’s research suggest the frontoparietal cortex does more than become more active when a task becomes difficult. Instead, the region changes how it communicates with other brain regions. This also depends on what information is needed at different decision-making stages.
Hwang notes, “If they always get it right, they know they’ve made the correct association, but once they start doing it wrong, they will have to guess, ‘Oh, did the context change, or did I not see the color clearly?’ That creates uncertainty.”
Hwang describes the brain’s “information hub” as a system that gathers information from different regions, determines what is relevant, and integrates those signals into a broader picture. One way to think of this function is as an air traffic controller, monitoring incoming information and adjusting communications as circumstances change.
“These are situations where people struggle with regulating their behavior. That, to me, is an integration problem. If that integration function is not working properly, then that could very likely mean they didn’t use the right context to regulate their behavior,” Hwang adds.
The study does not address how neurodiversity might affect this information-sorting process, although the findings could provide a foundation for researchers to investigate that question.
“It remains an open question how neurodiversity might affect frontoparietal integration. It is a very interesting question that, as far as I know, has not been studied directly, so I don’t have a definitive answer. One of our goals in conducting this study is to lay the foundation for future clinical investigations,” Hwang tells The Debrief in an email.
The findings suggest that the frontoparietal cortex can rapidly integrate and update information as circumstances change. Understanding this flexibility could eventually improve researchers’ understanding of neurological and psychiatric conditions involving behavioral regulation and decision-making. In particular, studying these communication patterns could help inform future investigations of conditions such as ADHD and schizophrenia, in which behavioral regulation and the use of contextual information can be impaired.
The new research was published in the Journal of Neuroscience.
Chrissy Newton is a PR professional and the founder of VOCAB Communications. She currently appears on The Discovery Channel and Max and hosts the Rebelliously Curious podcast, which can be found on YouTube and on all audio podcast streaming platforms. Follow her on X: @ChrissyNewton, Instagram: @BeingChrissyNewton, and chrissynewton.com. To contact Chrissy with a story, please email chrissy @ thedebrief.org.
Scientists from the Salk Institute have determined that brain waves in the visual cortex serve as a computational engine, allowing the brain to construct internal representations of the external world that enhance prediction, reconstruction, and perception capabilities.
While the scientists behind the new study focused their work on the visual cortex, they suspect that similar brain waves washing over other areas of the brain’s surface likely serve a similar role for other sensory systems.
The human brain uses electricity to communicate between synapses. Research has shown that this electrical activity can travel in waves across the brain’s surface. Called neural traveling waves, the phenomenon’s role in brain function and consciousness is not completely understood.
Previous studies have established that traveling brain waves play a significant role in behavior and attention. In 2020, Salk neuroscientist John Reynolds, PhD, successfully identified traveling brain waves in the visual systems of animals during a wakeful state.
According to a statement from Reynolds, the senior and co-corresponding author on the new paper, and colleagues, the 2020 research effort also found a direct correlation between traveling brain waves in the visual cortex and an animal’s ability to perceive objects directly in front of them. The authors suggest this discovery explained the “classic conundrum” of searching for something like a pair of keys or a phone that was right in front of you the whole time.
Although the connection between traveling brain waves and an awake animal’s ability to perceive objects seemed solid, Reynolds said he was left wondering why.
In their newly proposed theory, Reynolds and colleagues suggest that traveling brain waves are not simply “electrical noise” resulting from the brain’s normal relaying of signals. Instead, the Salk Institute team proposes that the neural connections responsible for the generation of traveling brain waves change their physiological structure, or “synaptic weights,” to more accurately reflect the outside world.
“Each sight, smell, sound, and action of an animal alters the connections that generate these waves, building the neural circuitry that the brain uses to construct an internal representation of the external world,” the team’s statement explains.
In the visual cortex, the part of the brain responsible for receiving and processing visual information, the team proposed that traveling brain waves perform four distinct functions. These include modulating visual perception from moment to moment and turning recent visual sensory inputs into “internal representations” of objects, people, and surroundings.
The team proposes that traveling brain waves also help humans generate short-term predictions about their surroundings, and “store and replay patterns that represent memories of events unfolding in time.” Reynolds said the process laid out by his team is analogous to how ChatGPT and other LLMs translate and interpret data.
“They learn statistical structure from language and use that knowledge to generate meaningful and appropriately structured text that reflects the patterns of language,” the researcher explained. “The brain may be doing something functionally similar—a biological generative model built from the ground up by experience.”
When detailing the potential impact of their proposed role for traveling brain waves in the visual cortex, the team highlights the contrast between a rich and complex world and its general predictability.
“Objects around you exist in 3D space, you see the world in retinal images that change with your eye and body movements, and the laws of physics and physiology overlay this all,” they explain.
Reynold’s team says that traveling brain waves are merely the brain’s way of internalizing these predictable “regularities” and encoding them in its synapse network. If correct, they said that this encoding would allow the brain to “infer the likely causes of sensory input and construct an internal model of the world.”
“This framing brings us one step closer to understanding how our brains compute the busy, messy world around us, turning a complicated sensory onslaught into behaviors and experiences,” they conclude.
The study “Neural traveling waves in cortex: network mechanisms and potential roles in neural computation” was published in Neuron.
Christopher Plain is a Science Fiction and Fantasy novelist and has spent the last six years as Associate News Editor and Head Science Writer at The Debrief. Follow and connect with him on X, learn about his books at plainfiction.com, or email him at christopher@thedebrief.org
New blood vessels flood the developing brain, then must be sculpted into a functional network. In the cortex, this pruning depends on selective elimination of redundant connections, but the cellular command center behind vascular refinement has remained only partly understood. A new study now points to microglia—the brain’s immune sentinels—as active architects of cerebrovascular pruning during postnatal development.
Using live visualization in the frontal cortex of postnatal day 11 mice, researchers tracked how microglia behave around forming blood vessels. They observed that microglia do not merely associate with vasculature; instead, they progressively migrate toward vessels as development proceeds. As vessel remodeling advances, microglia become enriched at sites where pruning occurs, suggesting a causal role rather than passive surveillance.
To test function, the team manipulated microglia–vessel interactions and assessed vascular outcomes. Intervening in microglial activity altered the extent of vessel elimination, consistent with the idea that microglia mediate pruning to refine the emerging vascular map. The results connect microglial behavior directly to the efficiency and organization of the developing cortical circulation.
Central to the mechanism is an immune signaling pathway previously linked to neuronal synaptic refinement: PD-L1 and its receptor PD-1. The study identifies PD-L1–PD-1 signaling as a regulator of microglia-driven vascular pruning. When this axis was disrupted, pruning was impaired, indicating that immune checkpoint-like communication can shape vascular architecture in the developing brain.
The authors further implicate a specific molecular source from microglia. They report that microglial CD5L secretion promotes the PD-1–dependent pruning program. In other words, microglia release CD5L, engage PD-1 signaling through PD-L1 interactions, and thereby influence which vessels persist and which are eliminated.
Collectively, the work reframes cerebrovascular pruning as a neuroimmune-guided developmental process. By showing that microglia actively target redundant vasculature and by defining a PD-L1–PD-1/CD5L pathway, the study provides mechanistic evidence for how immune cells can tune vascular networks to match developing brain circuitry.
Beyond development, the findings raise broader questions about whether similar immune checkpoint signaling contributes to abnormal vascular remodeling in disease, where pruning can be either excessive or insufficient. For now, the study delivers a clear developmental role: microglia help determine what the brain keeps growing and what it discards.
DOI: https://doi.org/10.1038/s41593-026-02378-x
Article Title: Microglia prune developing cortical blood vessels through PD-1 signaling.
Article References: Zhang, M., Wang, Y., Yang, R. et al. Microglia prune developing cortical blood vessels through PD-1 signaling. Nat Neurosci (2026). https://doi.org/10.1038/s41593-026-02378-x
Image Credits: AI Generated
Login