Schistosoma mansoni is a parasitic worm that infects millions of people worldwide, entering the body through the skin. Unlike bacterial infections that often cause pain and inflammation, S. mansoni usually slips in unnoticed, rarely causing discomfort. Scientists have long wondered why our skin’s defenses don’t react more strongly to this invader.

Researchers from the University of Pennsylvania and Tulane University explored whether a specialized group of pain-sensing neurons, called TRPV1+, plays a role in detecting and fighting off S. mansoni during its invasion. TRPV1+ neurons are nerve cells in the skin that respond to heat, spicy foods, and certain bacteria and fungi. When activated, they can trigger pain and release molecules that alert the immune system. Previous researchers have shown that these neurons help defend against bacterial and fungal skin infections, but their role in fighting off parasites was unclear. 

To examine how S. mansoni infects its hosts, the team conducted experiments using groups of 4 to 8 mice, matched for age and sex. They repeated each experiment 2 to 3 times to ensure their data was reproducible. They anesthetized the mice, exposed their ears to a solution containing 100 to 150 live S. mansoni larvae, and covered the area with vaseline to keep the solution in place. After 20 to 30 minutes, they counted the number of larvae remaining in the mice’s ears to assess how many had successfully penetrated their skin. 

Next, the team measured pain sensitivity in the mice exposed to the parasite by placing them in chambers and applying an infrared heat source to their paws. They recorded how long it took each mouse to withdraw its paw as a sign of pain. They repeated this test 3 times per paw on each mouse, waited at least 5 minutes between each measurement, and calculated an average withdrawal time. They found that mice infected with S. mansoni were approximately half as sensitive to heat-induced pain as an uninfected control group, suggesting that the parasite could be suppressing the mice’s TRPV1+ neurons.

To investigate this further, the team isolated nerve cells that transmit sensory signals from the mice’s skin, known as dorsal root ganglia, and grew them in the lab. They stimulated these neurons by adding a spicy compound in chili peppers, known as capsaicin. Then they measured calcium influx, a sign the neurons were active, using a special dye that glows differently under a microscope depending on calcium levels. This allowed them to see how active the neurons were and how many molecules they released in response to infection and stimulation. They found that 68% of neurons from uninfected mice responded to capsaicin, but only 26% of neurons from infected mice did so, confirming that the parasite dampened their sensory neuron responses.

To test whether restoring the mice’s neuron activity could help their bodies resist parasite invasion, the researchers genetically engineered the mice to produce a light-sensitive protein in their TRPV1+ neurons, called channelrhodopsin. They “turned on” these neurons by stimulating them with blue light for 30 minutes every day for 5 days before infecting the mice with parasites. Six days later, they assessed the mice’s immune response by using a laser to count immune cells in samples of ear tissue. They also determined how far the parasites had spread by counting larvae in lung samples. They saw that mice with the artificially activated TRPV1+ neurons had nearly double the immune response, blocked roughly twice as many larvae at the skin, and had about 20% fewer parasites in their lungs.

Next, the researchers selectively destroyed TRPV1+ neurons in a new set of mice using a compound known as resiniferatoxin. Three weeks later, they confirmed the treatment had worked by testing the mice’s pain sensitivity using the same heat assay as before. After confirming the mice had lost their pain sensitivity, the team exposed the mice to the parasites. They found that the reinfected mice had 1% to 3% weaker skin immune responses and approximately 25% to 30% more parasites in their lungs than a control group, further confirming that TRPV1+ neurons play a protective role during early infection.

The team concluded that S. mansoni has evolved ways to silence pain-sensing neurons, like TRPV1+. Their discovery suggests that future scientists could boost skin immunity against parasites by targeting sensory neurons. For example, they could develop topical creams or therapies that activate these neurons to help our bodies fight off S. mansoni and similar parasitic invaders.

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Scientists have often wondered how the brain can take in new experiences without erasing stored memories. However, a new study in Nature now identifies a circuit-level mechanism that may help answer this question—and it may also offer clues for improving artificial intelligence.

Researchers at NYU Langone Health recorded the activity of hundreds of neurons simultaneously across several brain regions in mice. By tracking how signals move from the hippocampus to the neocortex, where long-term memories are kept, they found that a subset of hippocampal neurons appears to participate in routing information between regions in distinct patterns. These cells participate in both incoming and outgoing signaling, but do so using distinct patterns of activity.

Separate Channels Through the Same Cells

The study focused on a series of interconnected brain regions: CA3, which processes rapidly changing information; CA1, which serves as a central hub; and the retrosplenial cortex, which is important for navigation and spatial memory. About one in four CA1 neurons receives most of the signals from CA3. When these same neurons send signals to the retrosplenial cortex, they fire in a different pattern, creating a separate outgoing channel using the same cells.

Rather than using new neurons, the brain separates these channels by changing how the same neurons fire together. The researchers suggest this arrangement may help reduce interference between new learning and more stable cortical memories.

“Our findings help explain how memory can be both moldable and enduring,” said co-lead author Joaquín Gonzalez, PhD, a postdoctoral fellow in the Department of Psychiatry at NYU Grossman School of Medicine. “By changing how the same cells fire together instead of turning on new cells, the brain can keep information organized and protect older memories.”

What Happens During Sleep

The CA1 neurons involved in learning during the day also stay active at night. The researchers found that these cells remain busy during sleep events called sharp-wave ripples, which are bursts of activity the hippocampus uses to replay and strengthen memories from the day.

Since overlapping neurons are recruited during both waking activity and sleep replay, the same circuit elements appear to participate in both learning and consolidation. This theoretically allows the brain to use a single system for both learning and storing memories, without the two processes interfering with each other.

“Our study shows how learning and memory consolidation can coexist in the same network,” said co-lead author Mihály Vöröslakos, MD, PhD. “Our discovery was made possible because for the first time, we were able to record hundreds of individual neurons across all the key regions simultaneously in animals that were moving around naturally.”

Implications for Disease and AI

The system identified in this research may help explain how memory disorders begin. In Alzheimer’s disease, for example, the hippocampal circuits examined here are some of the earliest to deteriorate. These networks are essential for sorting and organizing new experiences.

“Our discovery of a ‘memory switchboard’ deep in the hippocampus may provide clues as to how memory circuits fail in Alzheimer’s disease,” said co-senior author Zhe S. Chen, PhD, a professor in the Departments of Psychiatry and Neuroscience at NYU Grossman School of Medicine.

Artificial intelligence systems have a hard time holding onto what they’ve already learned when faced with new tasks, a problem researchers call catastrophic forgetting. The human brain appears able to update memories without catastrophic forgetting by altering the use of existing neural circuits. By studying how our brains pull this off, scientists hope to design AI that can keep learning new things without forgetting the old.

“By showing how the mammalian brain can safeguard memories during learning, our research may offer a biological blueprint for designing next-generation AI technology that can update itself continuously without overwriting what it has already acquired,” said co-senior author György Buzsáki, MD, PhD, the Biggs Professor of Neuroscience at NYU Grossman School of Medicine.

The researchers plan to investigate whether similar switchboard-like channels exist in other memory circuits. The authors caution that their findings in mice under controlled conditions do not yet allow conclusions about the human brain.

Austin Burgess is a writer and researcher with a background in sales, marketing, and data analytics. He holds an MBA, a Bachelor of Science in Business Administration, and a data analytics certification. His work focuses on breaking scientific developments, with an emphasis on emerging biology, cognitive neuroscience, and archaeological discoveries.