The achievement gives scientists a new way to examine how the brain and body work together to produce complex actions, including walking and flying. It also opens the door to broader studies of the core rules that govern nervous systems.

“We can see all of the neurons and their connections as a complete unit for the first time and ask, ‘What do we learn from that?'” said study co-senior author Rachel Wilson, the Joseph B. Martin Professor of Basic Research in the Field of Neurobiology in the Blavatnik Institute at HMS.

First Complete Fruit Fly Brain and Body Wiring Map

The new map of neural connections, known as a connectome, extends a previously published fruit fly brain connectome by adding the fly’s spinal cord equivalent, called the nerve cord.

“It is really important to have a central nervous system connectome that is as complete as possible so we can link up the brain and body and start thinking about behavior holistically,” said study co-senior author Wei-Chung Allen Lee, associate professor of neurobiology at HMS and HMS professor of neurology at Boston Children’s Hospital.

When the team studied the connectome, they discovered that many fruit fly behaviors appear to be directed by local neural circuits in the relevant body parts, rather than by one central command area in the brain.

The full connectome is now freely available online, giving researchers around the world a powerful new resource for neuroscience studies. The work, published June 8 in Nature, received support in part from U.S. federal funding, including the BRAIN Initiative (Brain Research Through Advancing Innovative Neurotechnologies), National Institutes of Health, and National Science Foundation.

Why Fruit Flies Matter in Neuroscience

One of neuroscience’s major unanswered questions is how neurons in the brain and body connect and coordinate to generate behavior. The fruit fly Drosophila melanogaster is a valuable model for exploring that problem.

Fruit flies are simple to breed and keep in the lab. Although their nervous system contains only about 160,000 neurons, they can still perform complex behaviors such as navigating, interacting socially, learning, and reacting to sensory signals. They also have what Lee describes as an incredibly sophisticated genetic toolkit, which allows scientists to access, control, and record activity from single neurons or groups of neurons.

In 2024, the FlyWire Consortium, led by Mala Murthy and Sebastian Seung at Princeton, who are also co-authors of the new study, published a complete connectome of a fruit fly brain. At the same time, Lee and his colleagues were building a connectome of the fruit fly nerve cord, which controls the legs, wings, and other appendages while also processing sensory information.

“The brain and nerve cord connectomes are each useful on their own, but until you can bridge the two, it’s hard to understand how information moves between the brain and the body,” said co-first author Helen Yang, a research fellow in neurobiology in the Wilson Lab.

Co-first author Alexander Bates, also a research fellow in neurobiology in the Wilson Lab, noted that the brain holds most of the neurons, but the nerve cord contains neurons that are “some of the most useful” because they are tied to sensation, movement, and functions that are often easier to interpret.

Connecting the Brain to the Nerve Cord

The FlyWire team was eager to shift toward the brain and neural cord, or BANC, dataset imaged in the Lee Lab, said co-senior author Murthy, the Karol and Marnie Marcin ’96 Professor of Neuroscience at Princeton and director of the Princeton Neuroscience Institute (PNI).

“The new connectome represents a major advance for the field, with the ability to understand how circuits in the brain receive feedback from and control the actions of the body,” she said.

“For the first time, we can follow information flow from sensation to action across an entire nervous system,” added co-author Arie Matsliah of the PNI.

How Scientists Built the Connectome

To create the connectome, researchers sliced a single fruit fly into thousands of extremely thin serial sections. They then used electron microscopy to capture millions of images showing neurons and their connections. AI tools helped align those images and assemble them into a unified 3D map.

The finished connectome shows how each neuron connects with other neurons in the brain and nerve cord at the level of individual synapses. The map does not cover the fly’s entire body, but the researchers used identifiable neurons and previous scientific literature to link central nervous system neurons with neurons in many appendages and sensory organs, effectively “embodying” the connectome.

Lee said scientists can use the connectome to develop new hypotheses for lab experiments. He compares it to having detailed Google Maps information while planning a route.

“The connectome has shown us that most of our hypotheses are too simple. Now, we can develop more complex hypotheses and move forward with experiments to test them,” Lee said.

A Surprise About How Movement Is Controlled

The researchers have already used the connectome to study motor control, especially how a fly moves its legs and other body parts.

A long-standing idea in neuroscience holds that the brain acts as a centralized controller that decides which actions an animal will perform. The fruit fly connectome pointed to a different answer.

The team found that motor control in fruit flies mostly occurs locally. For instance, movement of one leg is mainly governed by the neural circuits for that leg. Those circuits then communicate with circuits for the other legs to produce coordinated actions such as walking.

The same pattern appeared in circuits linked to the fly’s wings, mouth, and other body parts. The researchers also found that motor circuits connect with other circuit types, including those in the visual and endocrine systems, which supply extra information that helps shape behavior.

“Our findings suggest that control for actions is highly distributed in local modules that link up and work together in different ways,” Bates said.

What Comes Next for Connectome Research

The researchers say the connectome could support many future lines of investigation. Yang compares it to the Human Genome Project, another large-scale open resource that has been used in many different ways.

Soon, the team plans to add more information to the connectome, including details about neuropeptides, the small, protein-like molecules that neurons use to communicate.

The connectome may also reveal basic principles that apply to nervous systems across species, including humans. Bates said many discoveries from fruit fly neuroscience have carried over from invertebrates to mammals, including findings related to navigation, olfaction, and memory.

Another goal is “to bring full-connectome mapping to much more complex organisms,” said Matsliah. He noted that progress in AI, computing, and open collaborative science is making this kind of research increasingly possible.

A major question now is whether the distributed neural control observed in fruit flies is also found in other animals. Lee is currently investigating that possibility in mice.

“I would be shocked if this is unique to the fly,” Yang said. “We don’t have this level of resolution in other animals, but we know that they have a lot of these local circuits.”

Lessons for Artificial Intelligence

The work could also have implications for artificial intelligence. The connectome offers real biological data that may help guide the design of artificial agents that move through virtual worlds, systems that are increasingly used to study intelligence and improve AI training.

“One thing that always amazes me is that this tiny little fly does a hell of a lot; even our best AI agents and robots can’t do everything that a fly does,” Yang said. “There may be lessons for AI in how the nervous system is organized.”

Authorship, funding, disclosures

Jasper S. Phelps and Minsu Kim are also co-first authors of the study. Jan Drugowitsch is co-senior author. Additional authors include Zaki Ajabi, Eric Perlman, Kevin M. Delgado, Mohammed Abdal Monium Osman, Christopher K. Salmon, Jay Gager, Benjamin Silverman, Sophia Renauld, Farzaan Salman, Janki Patel, Matthew F. Collie, Jingxuan Fan, Diego A. Pacheco, Yunzhi Zhao, Wenyi Zhang, Laia Serratosa Capdevila, Ruairí J.V. Roberts, Eva J. Munnelly, Nina Griggs, Helen Langley, Borja Moya-Llamas, Zuoyu Zhang, Ryan T. Maloney, Szi-chieh Yu, Amy R. Sterling, Marissa Sorek, Krzysztof Kruk, Nikitas Serafetinidis, Serene Dhawan, Finja Klemm, Paul Brooks, Ellen Lesser, Jessica M. Jones, Sara E. Pierce-Lundgren, Su-Yee Lee, Yichen Luo, Andrew P. Cook, Theresa H. McKim, Dimitrios Stasi Giakoumas, Benjamin Gorko, Emily C. Kophs, Tjalda Falt, Alexa M. Negron-Morales, Austin Burke, James Hebditch, Kyle P. Willie, Ryan Willie, Sergiy Popovych, Nico Kemnitz, Dodam Ih, Kisuk Lee, Ran Lu, Akhilesh Halageri, J. Alexander Bae, Ben Jourdan, Gregory Schwartzman, Damian D. Demarest, Emily Behnke, Doug Bland, Anne Kristiansen, Jaime Skelton, Tom Stocks, Dustin Garner, Anthony Hernandez, Sandeep Kumar, The BANC-FlyWire Consortium, Kevin C. Daly, Sven Dorkenwald, Forrest Collman, Marie P. Suver, Lisa M. Fenk, Michael J. Pankratz, Zepeng Yao, Stephen J. Huston, Tomke Stürner, Gregory S.X.E. Jefferis, Katharina Eichler, Andrew M. Seeds, Stefanie Hampel, Sweta Agrawal, Tatsuo S. Okubo, Meet Zandawala, Thomas Macrina, Diane-Yayra Adjavon, Jan Funke, John C. Tuthill, Anthony Azevedo, and Benjamin L. de Bivort.

Funding was provided by the National Institutes of Health (grants R01NS121874; RF1MH117808; U19NS118246; U24NS126935; RF1MH117815; K99NS129759; R00NS117657; R01NS102333; RF1NS128785; R01NS140174; UM1NS132253; U24NS13992; RF1MH128840; R01NS121911; T32GM144273; R01DK139131; R25NS080687), a Sir Henry Wellcome Postdoctoral Fellowship (222782/Z/21/Z), a Smith Family Foundation Odyssey Award, a Harvard/MIT Joint Research Grant, an HHMI Life Sciences Research Foundation Postdoctoral Fellowship (PJ100000343), a New York Stem Cell Foundation Robertson Neuroscience Investigator Award, the Deutsche Forschungsgemeinschaft (ZA1296/1-1; EXC2151-390873048; PA787/7-3; PA787/9-3), the Nevada IDeA Network of Biomedical Research Excellence (GM103440), the National Science Foundation (2127379; 2014862), the Japan Society for the Promotion of Science (KAKENHI 25K00370), the Japan Science and Technology Agency (ASPIRE JPMJAP2302; CRONOS JPMJCS24K2), an HHMI Gilliam Fellowship (GT15790), the Max Planck Society, the Shanahan Family Foundation, a Kempner Graduate Fellowship, the Medical Research Council (MC_EX_MR/T046279/1), the Alice and Joseph Brooks Fund, and the Beijing Natural Science Foundation (IS23084). The authors also acknowledge that the work benefited from the O2 High-Performance Compute Cluster, supported by the Research Computing Group at HMS.

Harvard University filed a patent application for GridTape (WO2017184621A1) on behalf of the inventors, including W. Lee, and negotiated licensing agreements with interested partners. Macrina, Popovych, Kemnitz, Ih, K. Lee, Lu, Halageri, Bae, and Seung declare financial interest in Zetta AI. Seung declares financial interest in Memazing, Inc. Capdevila, Roberts, Langley, Munnelly, Griggs, and Moya-Llamas declare financial interest in Aelysia Ltd. Perlman is a principal of Yikes LLC.

Susan Bianco, 87, of Lancaster, first realized her hearing was changing when conversations became more difficult.

She often found herself asking her husband to repeat what he said. Phone calls became challenging, and noisy social settings were especially frustrating.

“It’s very hard to hear in a crowd,” she said. “I can’t understand what one person is saying if other people are talking.”

Later, she began noticing another symptom. A buzzing noise in her ears would appear and become more noticeable whenever she felt tired.

Bianco’s experience is common. According to the Centers for Disease Control and Prevention, about 13% of U.S. adults have hearing difficulties. Among adults age 65 and older, that number rises to 27%. Around 10% of adults also experience tinnitus, a condition commonly associated with hearing loss that causes sounds such as ringing or buzzing in the ears.

The likelihood of developing hearing loss or tinnitus increases with age and exposure to loud noise.

“You can’t stop aging, but you can take steps to conserve your hearing and reduce your risk of developing hearing loss and tinnitus,” said Dr. Jackie Price, an audiologist at Penn State Health Otolaryngology — Head and Neck Surgery.

October is National Protect Your Hearing Month. Price explains what causes tinnitus, how hearing can be protected, and when it may be time to seek help.

What Is Tinnitus?

Tinnitus is the perception of sound when no external sound source is present. People often describe it as ringing, buzzing, hissing, or whooshing in one or both ears.

Some individuals compare the noise to cicadas or even a passing freight train, Price said.

“For some people, the noise is constant and bothersome, interfering with their productivity and quality of life,” Price said.

The sounds are not coming from the environment around you. Instead, they result from a communication problem between the ears and the brain.

Other sound-related conditions can occur as well. Hyperacusis causes everyday noises to seem unusually loud or overwhelming. Misophonia triggers strong emotional reactions to certain sounds.

How Hearing Loss and Tinnitus Develop

According to Price, tinnitus and similar sound disorders are frequently among the earliest signs of hearing loss.

The process often begins inside the cochlea, a spiral-shaped structure in the inner ear. Tiny sensory hair cells located there convert sound vibrations into signals that travel to the brain.

When those delicate cells become damaged, they can no longer transmit information properly. As hearing ability declines, communication between the ears and brain may also become distorted, contributing to the phantom sounds associated with tinnitus.

The effects can extend far beyond hearing itself.

Hearing loss and tinnitus have been linked to problems with sleep, concentration, and personal relationships. Research also shows they may contribute to faster cognitive decline, a higher risk of depression, and an increased likelihood of falls.

How To Protect Your Hearing

One of the most effective ways to reduce the risk of hearing damage is to limit exposure to loud noise.

Price recommends using hearing protection whenever sound levels exceed 85 decibels. Situations such as concerts, sporting events, fireworks displays, and power tool use can all expose people to potentially harmful noise levels.

“I counsel people to wear hearing protection when they’re mowing grass instead of listening to music through earbuds,” Price said. “It’s like a double whammy because people have the noise from the mower, and then they crank up the music so they can hear it, and then they listen to excess noise for 45 minutes or more, sometimes twice a week.”

Choosing effective hearing protection is also important. Earplugs and earmuffs should have a Noise Reduction Rating of at least 22 decibels. This rating, displayed on product packaging, indicates how much noise the product can reduce.

Proper insertion matters as well.

“Take a foam earplug between your two fingers and smoosh it down and roll it,” Price explained. “Then, when you go to put it in your ear, pull on your ear lobe with the opposite hand to open up the ear canal, insert the earplug and let it fully expand.”

Most foam earplugs are designed for one-time use to ensure they maintain a tight seal against noise.

Treatment Options for Hearing Loss and Tinnitus

Although there is currently no cure for hearing loss or tinnitus, available treatments can help improve daily functioning and quality of life.

For hearing loss, treatment depends on the cause and severity. Hearing aids and other assistive technologies are often recommended to improve communication.

For tinnitus, one option is Tinnitus Retraining Therapy. This approach combines counseling and sound therapy to help people reduce the impact of the condition.

Counseling helps patients better understand and cope with tinnitus. Sound therapy uses gentle background noise to draw attention away from the ringing or buzzing sensation.

Bianco recently began Tinnitus Retraining Therapy and now wears hearing aids.

As part of her treatment, Price programmed a soft, continuous sound into Bianco’s hearing aid. The goal is to make the tinnitus less distracting.

“It sounds like it’s raining, which is a sound I don’t mind too much,” Bianco said.

When To Get a Hearing Test

Anyone experiencing ringing or other unusual sounds in their ears should consider a hearing evaluation, Price said.

“Sometimes people think they hear fine, but there are signs of change inside the ear, such as hair cell damage or hearing loss at the highest frequencies,” Price said. “Testing can help you become better educated about what’s going on so you can manage those changes.”

Even when hearing problems are not obvious, testing can reveal early signs of damage and provide an opportunity to take steps that may help preserve hearing and improve long-term quality of life.

That mystery was ultimately explained by a recalculation of Neptune’s mass in the 1990s, but then a new theory of a potential planet nine was put forward in 2016 by astronomers Konstantin Batygin and Mike Brown at Caltech (the California Institute of Technology).

Their theory relates to the Kuiper Belt, a giant belt of dwarf planets, asteroids and other matter that lies beyond Neptune (and includes Pluto). Many Kuiper Belt objects – also referred to as trans-Neptunian objects – have been discovered orbiting the Sun, but like Uranus they don’t do so in a continuous expected direction. Batygin and Brown argued that something with a large gravitational pull must be affecting their orbit, and proposed planet nine as a potential explanation.

This would be comparable to what happens with our own Moon. It orbits the Sun every 365.25 days, in line with what you would expect in view of their distance apart. However, the Earth’s gravitational pull is such that the Moon also orbits the planet every 27 days. From the point of view of an outside observer, the Moon moves in a spiraling motion as a result. Similarly, many objects in the Kuiper Belt show signs of their orbits being affected by more than just the Sun’s gravity.

While astronomers and space scientists were initially skeptical about the planet nine theory, there has been mounting evidence thanks to increasingly powerful observations that the orbits of trans-Neptunian objects are indeed erratic. As Brown said in 2024:

“I think it is very unlikely that P9 does not exist. There are currently no other explanations for the effects that we see, nor for the myriad other P9-induced effects we see on the Solar System.”

In 2018, for example, it was announced that there was a new candidate for a dwarf planet orbiting the Sun, known as 2017 OF201. This object measures around 700km across (Earth is roughly 18x bigger) and has a highly elliptical orbit. This lack of a roughly circular orbit around the Sun suggested either an impact early in its lifetime that put it on this path, or gravitational influence from planet nine.

Problems with the theory

On the other hand, if planet nine exists, why hasn’t anyone found it yet? Some astronomers question whether there’s enough orbital data from Kuiper objects to justify any conclusions about its existence, while alternative explanations get put forward for their motion, such as the effect of a ring of debris or the more fantastical idea of a small black hole.

The biggest issue, however, is that the outer Solar System just hasn’t been observed for long enough. For example, object 2017 OF201 has an orbital period of about 24,000 years. While an object’s orbital path around the Sun can be found in a short number of years, any gravitational effects probably need four to five orbits to notice any subtle changes.

New discoveries of objects in the Kuiper Belt have also presented challenges for the planet nine theory. The latest is known as 2023 KQ14, an object discovered by the Subaru telescope in Hawaii.

It is known as a “sednoid,” meaning it spends most of its time far away from the Sun, though within the vast area in which the Sun has a gravitational pull (this area lies some 5,000AU or astronomical units away, where 1AU is the distance from the Earth to the Sun). The object’s classification as a sednoid also means the gravitational influence of Neptune has little to no effect on it.

2023 KQ14’s closest approach to the Sun is around 71AU away, while its furthest point is about 433AU. By comparison, Neptune is about 30AU away from the Sun. This new object is another with a very elliptical orbit, but it is stabler than 2017 OF201, which suggests that no large planet, including a hypothetical planet nine, is significantly affecting its path. If planet nine exists, it would therefore perhaps have to be farther than 500AU away from the Sun.

To make matters worse for the planet nine theory, this is the fourth sednoid to be discovered. The other three also exhibit stable orbits, similarly suggesting that any planet nine would have to be very far away indeed.

Nonetheless, the possibility remains there could still be a massive planet affecting the orbits of bodies within the Kuiper Belt. But astronomers’ ability to find any such planet remains somewhat limited by the restrictions of even unmanned space travel. It would take 118 years for a spacecraft to travel far enough away to find it, based on estimates from the speed of Nasa’s New Horizons explorer.

This means we’ll have to continue to rely on ground- and space-based telescopes to detect anything. New asteroids and distant objects are being discovered all the time as our observing capabilities become more detailed, which should gradually shed more light on what might be out there. So watch this (very big) space, and let’s see what emerges in the coming years.

The affected area is known as the PrK transfer tunnel. NASA and Roscosmos have been monitoring the leak for years while working to understand its root cause and reduce the loss of air. Roscosmos has used both temporary and permanent sealants as part of its leak mitigation efforts.

Leak Rate Rises During Progress 95 Operations

According to NASA’s latest update, Roscosmos detected a higher leak rate during cargo operations involving the Progress 95 spacecraft during the week of June 1. The leak rate increased to about two pounds per day, and engineers identified new suspected leak areas inside the PrK.

Following those findings, Roscosmos decided on Friday morning to prepare for a more extensive inspection and structural repair effort. The revised plan included cutting a bracket to improve access to an area that may have been contributing to the leak. NASA noted that this method could have increased the risk to the surrounding structure.

Astronauts Enter Safe Haven as Precaution

Because of the potential structural risk, NASA directed the four SpaceX Crew-12 members and NASA astronaut Chris Williams to take a heightened safety posture known as a safe haven. Williams traveled to the station aboard the Soyuz MS-28 spacecraft.

As a precaution, the astronauts sheltered inside the SpaceX Dragon spacecraft while the repair procedure was being evaluated.

Roscosmos Pauses Repair Work for More Data

Later Friday morning, Roscosmos chose not to proceed with the structural repair work. Instead, teams paused the operation to gather more measurements and review additional data.

The follow-up work included inspecting suspected areas of interest and reviewing places where sealant had already been applied. NASA strongly supported the decision to collect more information before moving ahead.

After Roscosmos paused the repair effort, Crew-12 and Williams ended their safe haven activities and returned to normal operations aboard the orbiting laboratory.

NASA said it will continue working with Roscosmos and the space station’s other international partners to assess the situation and ensure the leak issue is resolved.

The compound, known by researchers as “Compound 10,” is the result of nearly two decades of work led by Ursula Quitterer, Professor of Molecular Pharmacology at ETH Zurich.

A Long Search for New Alzheimer’s Clues

The research began almost 20 years ago when Quitterer received brain tissue samples from a colleague at Ain Shams University Hospital in Cairo. The samples were collected during tumor surgeries and came from both people with dementia and individuals without the condition.

Those samples helped launch an investigation into a protein called GRK2, which has been the focus of Quitterer’s research for many years.

GRK2 plays an important role throughout the body. As a regulatory protein, it helps cells respond to signals and adapt to stress. It is active in several organs, including the heart and the brain, where it supports healthy nerve cell function.

Using both human brain tissue and mouse models of Alzheimer’s disease, the ETH Zurich team uncovered evidence that GRK2 may be a major contributor to dementia. Their findings were recently published in the journal Cell Reports Medicine.

When a Protective Protein Turns Harmful

GRK2 exists in two forms inside cells. One form functions normally, while the other becomes inactive through cellular processes.

The researchers found that the inactive version accumulates in large amounts in the brains of people with dementia. Similar patterns were also observed in mice that develop Alzheimer’s-like symptoms.

Further experiments revealed that inactive GRK2 molecules clump together inside nerve cells. These clusters attach to mitochondria, the structures often referred to as the “powerhouses” of cells, and interfere with their function.

“The GRK2 aggregates block the pores of the mitochondria, reducing the amount of energy they can supply and leading to a situation of stress inside the cells,” Quitterer explains.

The team also found that inactive GRK2 appears to increase the production of amyloid beta, a protein fragment widely associated with Alzheimer’s disease.

This creates a damaging cycle. Amyloid beta places additional stress on nerve cells, which leads to the formation of even more inactive GRK2. As more GRK2 accumulates and forms aggregates, the disease process continues to accelerate.

Compound 10 Breaks the Cycle

To interrupt this cycle, the researchers designed and tested several experimental compounds in cell cultures and mice.

Among them, Compound 10 delivered the strongest results. The compound prevented GRK2 molecules from forming harmful aggregates, allowing mitochondria to function more effectively. As a result, amyloid beta deposits were reduced, nerve cells remained healthier, and cell death was slowed.

The benefits extended beyond the brain.

In mice, Compound 10 also appeared to improve heart function and influence aging-related changes. The researchers observed that treated animals developed fewer gray hairs as they grew older.

Why the Research Took Nearly Two Decades

The team has completed the basic research phase and filed a patent application for Compound 10.

According to Quitterer, one reason the work took so long is the nature of Alzheimer’s research itself.

“It took so long simply because everything takes so long in Alzheimer’s research,” explains Quitterer.

Because Alzheimer’s is an age-related disease, the researchers worked with older mice. These animals were typically between one and a half and two years old. Each experiment required a similar amount of time before meaningful conclusions could be drawn and the next stage of research could begin.

“It’s all a great deal slower than in cancer research, for example.”

A New Target for Future Alzheimer’s Treatments

ETH Zurich and the researchers are now seeking a company interested in advancing Compound 10 toward drug development.

“Alzheimer’s is a very complex disease,” says Quitterer. Current medications do not cure the disease, but rather — at most — delay its progression by several months.

“That’s why it’s so important that we’ve now identified a new target protein in the form of GRK2, as well as an active ingredient that operates via GRK2 and therefore via a different mechanism than existing Alzheimer’s drugs.”

While much more research is needed before the compound could be tested in people, the discovery opens the door to a new treatment strategy. Researchers believe that combining Compound 10 with existing Alzheimer’s medications could eventually provide greater benefits and improve quality of life for patients.