The study acquainted 49 bats with a series of ringtones that attracted their attention, and trained them to associate flying toward just one of the tones with a reward: a baitfish snack.

Between one and four years later, eight of those bats were recaptured and exposed again to the food-related ringtone. All of them flew toward the sound, and six flew all the way to the speaker and grabbed the food reward, meaning they expected to find food. Control bats without previous training on the sounds were comparatively unmoved by the exposure to the unfamiliar tones.

“I was surprised — I went into this thinking that at least a year would be a reasonable time for them to remember, given all the other things they need to know and given that long-term memory does have real costs. Four years strikes me as a long time to hold on to a sound that you might never hear again,” said lead author May Dixon, a postdoctoral scholar in evolution, ecology and organismal biology at The Ohio State University.

Dixon led this study at the Smithsonian Tropical Research Institute in Panama while she was a graduate student at the University of Texas at Austin.

“The environment that previous generations experienced can be extremely different from the environment an animal is born into — and it may also change throughout an animal’s life,” she said. “Trying to figure out how animals use learning and memory is one way to figure out how they’re going to make it in a life full of change in the modern world.”

The study is published today (June 20, 2022) in Current Biology.

In the first phase, individual frog-eating bats captured for a series of cognition tests were exposed to a highly attractive sound in the lab: the mating call of the male túngara frog, one of this species of bats’ preferred prey. Flying to that sound was rewarded with a piece of baitfish placed on mesh above the speaker.

Over time, the sound was mingled with and gradually replaced by a ringtone, but the reward was the same. Researchers then introduced three other ringtones, none of which was connected to a food reward. Bats were trained to discern the differences and eventually no longer flew toward the unrewarded sounds. Each bat secured at least 40 snacks by flying to the trained ringtone over 11 to 27 days. All bats were microchipped and returned to the wild.

Beginning a year later and for three additional years, Dixon captured bats and identified eight from the initial trial by their microchips. In a follow-up test of their response to the original rewarded ringtone, all eight trained bats quickly flew to the sound and were able to tell the difference between that ringtone and a new, steady tone, though many of the bats did fly to an unrewarded sound from the initial training.

When 17 untrained bats were exposed to these sounds, they mostly twitched their ears in response to the sounds, but didn’t fly toward them.

“The study taught us a lot because there are relatively few studies of long-term memory in wild animals and we don’t have systematic understanding of long-term memories in nature yet,” Dixon said. “If we can collect additional data on different species of bats, we could pick this apart and see what life histories select for long memories.”

The paper lists 39 previous studies that have documented memory in species ranging from fish, birds and bats to goats and primates. Some of the longest of those experiments — documenting memory in sea lions for 10 years, tortoises for nine years and dolphins for 20 years — were all conducted on animals that lived in captivity the entire time.

“Being able to study memory in the wild is important,” said study co-author Gerald Carter, assistant professor of evolution, ecology and organismal biology at Ohio State. “You can’t necessarily extrapolate from the wealth of data we have on animals in the lab to what they’re facing in the wild, where there are many more things they have to remember. The environment is different and the brain is different in the wild versus captivity.”

Despite the human tendency to assume a long memory gives our species the intelligence advantage, nature shows us that memory flexibility — also called adaptive forgetting — may be important for survival.

“It’s not always true that being the smartest or having the longest memory is actually advantageous. Research has shown that fruitflies selected for improved memories can’t compete as well against other fruitflies,” Dixon said. “Just because it’s useful for humans to be so smart and have such good memories doesn’t necessarily mean it’s going to be the best thing for other animals.

“That’s why we want to figure out when these skills are actually going to help animals and when they could be a liability.”

This work was supported by the National Science Foundation and the Smithsonian Tropical Research Institute (STRI). Co-authors include Patricia Jones of Bowdoin College, Michael Ryan of STRI and UT Austin, and Rachel Page of STRI.

As light passes through the slide, an image of Australia can be seen, but when you flip the slide and look again, an image of the Sydney Opera House is visible. The pair of images created is just one example of an untapped number of possibilities.

The ability to produce two distinctly different images is possible thanks to the ANU scientists’ ability to control the direction in which light can and can’t travel at the nanoscale. The development could pave the way for new light-based devices that could lead to faster, cheaper and more reliable Internet. It could also serve as the foundation for many of the technologies of tomorrow.

Developed in collaboration with colleagues from China, Germany and Singapore, the new technology uses nanoparticles, so small that about 12,000 of them can fit within a cross-section of a human hair. These tiny particles are arranged into unique patterns on the slides.

“The particles control the flow of light like road signs control traffic on a busy road by manipulating the direction in which light can, or can’t, travel,” project leader Dr Sergey Kruk said.

“Some particles allow light to flow from left to right only, others from right to left or the pathway might be blocked in either direction.”

Dr Lei Wang, from Southeast University in China said: “While the purpose of these images is mainly artistic, they demonstrate the potential for this new technology.

“In real-world applications these nanoparticles can be assembled into complex systems that would control the flow of light in a useful manner — such as in next-generation communications infrastructure.”

According to Dr Kruk, the ability to control the flow of light at the nanoscale ensures light “goes where it’s supposed to go and doesn’t go where it’s not supposed to.”

“We exchange enormous amounts of information with the help of light. When you make a video call, say, from Australia to Europe, your voice and image get converted into short pulses of light that travel thousands of kilometres through an optical fibre over the continents and oceans,” Dr Kruk, from the ANU Nonlinear Physics Centre, said.

“Unfortunately, when we use current light-based technologies to exchange information a lot of parasitic effects might occur. Light might get scattered or reflected, which compromises your communication.

“By ensuring light flows exactly where it needs to flow, we would resolve many issues with current technologies.”

According to Dr Kruk, the development of many technologies of tomorrow will rely heavily on our ability to control light at a tiny scale.

“A wide deployment of tiny components that can control the flow of light could potentially bring technological and social changes similar to transformations brought about in the past by the development of tiny components that control the flow of electricity, which are known as diodes and transistors,” he said.

“Control over the flow of electricity at the nanoscale is what ultimately brought us modern computers and smartphones. It is therefore exciting to envision the potential of our emerging technology for controlling flow of light.”

This research was a collaboration between the Nonlinear Physics Centre at the ANU Research School of Physics, Paderborn University in Germany, Southeast University in China and A*STAR Singapore.

Distinguishing these harmful driver mutations from the neutral passengers could help researchers identify better drug targets. To boost those efforts, an MIT-led team has built a new computer model that can rapidly scan the entire genome of cancer cells and identify mutations that occur more frequently than expected, suggesting that they are driving tumor growth. This type of prediction has been challenging because some genomic regions have an extremely high frequency of passenger mutations, drowning out the signal of actual drivers

“We created a probabilistic, deep-learning method that allowed us to get a really accurate model of the number of passenger mutations that should exist anywhere in the genome,” says Maxwell Sherman, an MIT graduate student. “Then we can look all across the genome for regions where you have an unexpected accumulation of mutations, which suggests that those are driver mutations.”

In their new study, the researchers found additional mutations across the genome that appear to contribute to tumor growth in 5 to 10 percent of cancer patients. The findings could help doctors to identify drugs that would have greater chance of successfully treating those patients, the researchers say. Currently, at least 30 percent of cancer patients have no detectable driver mutation that can be used to guide treatment.

Sherman, MIT graduate student Adam Yaari, and former MIT research assistant Oliver Priebe are the lead authors of the study, which appears today in Nature Biotechnology. Bonnie Berger, the Simons Professor of Mathematics at MIT and head of the Computation and Biology group at the Computer Science and Artificial Intelligence Laboratory (CSAIL), is a senior author of the study, along with Po-Ru Loh, an assistant professor at Harvard Medical School and associate member of the Broad Institute of MIT and Harvard. Felix Dietlein, an associate professor at Harvard Medical School and Boston Children’s Hospital, is also an author of the paper.

A new tool

Since the human genome was sequenced two decades ago, researchers have been scouring the genome to try to find mutations that contribute to cancer by causing cells to grow uncontrollably or evade the immune system. This has successfully yielded targets such as epidermal growth factor receptor (EGFR), which is commonly mutated in lung tumors, and BRAF, a common driver of melanoma. Both of these mutations can now be targeted by specific drugs.

While those targets have proven useful, protein-coding genes make up only about 2 percent of the genome. The other 98 percent also contains mutations that can occur in cancer cells, but it has been much more difficult to figure out if any of those mutations contribute to cancer development.

“There has really been a lack of computational tools that allow us to search for these driver mutations outside of protein-coding regions,” Berger says. “That’s what we were trying to do here: design a computational method to let us look at not only the 2 percent of the genome that codes for proteins, but 100 percent of it.”

To do that, the researchers trained a type of computational model known as a deep neural network to search cancer genomes for mutations that occur more frequently than expected. As a first step, they trained the model on genomic data from 37 different types of cancer, which allowed the model to determine the background mutation rates for each of those types.

“The really nice thing about our model is that you train it once for a given cancer type, and it learns the mutation rate everywhere across the genome simultaneously for that particular type of cancer,” Sherman says. “Then you can query the mutations that you see in a patient cohort against the number of mutations you should expect to see.”

The data used to train the models came from the Roadmap Epigenomics Project and an international collection of data called the Pan-Cancer Analysis of Whole Genomes (PCAWG). The model’s analysis of this data gave the researchers a map of the expected passenger mutation rate across the genome, such that the expected rate in any set of regions (down to the single base pair) can be compared to the observed mutation count anywhere across the genome.

Changing the landscape

Using this model, the MIT team was able to add to the known landscape of mutations that can drive cancer. Currently, when cancer patients’ tumors are screened for cancer-causing mutations, a known driver will turn up about two-thirds of the time. The new results of the MIT study offer possible driver mutations for an additional 5 to 10 percent of the pool of patients.

One type of noncoding mutation the researchers focused on is called “cryptic splice mutations.” Most genes consist of sequences of exons, which encode protein-building instructions, and introns, which are spacer elements that usually get trimmed out of messenger RNA before it is translated into protein. Cryptic splice mutations are found in introns, where they can confuse the cellular machinery that splices them out. This results in introns being included when they shouldn’t be.

Using their model, the researchers found that many cryptic splice mutations appear to disrupt tumor suppressor genes. When these mutations are present, the tumor suppressors are spliced incorrectly and stop working, and the cell loses one of its defenses against cancer. The number of cryptic splice sites that the researchers found in this study accounts for about 5 percent of the driver mutations found in tumor suppressor genes.

Targeting these mutations could offer a new way to potentially treat those patients, the researchers say. One possible approach that is still in development uses short strands of RNA called antisense oligonucleotides (ASOs) to patch over a mutated piece of DNA with the correct sequence.

“If you could make the mutation disappear in a way, then you solve the problem. Those tumor suppressor genes could keep operating and perhaps combat the cancer,” Yaari says. “The ASO technology is actively being developed, and this could be a very good application for it.”

Another region where the researchers found a high concentration of noncoding driver mutations is in the untranslated regions of some tumor suppressor genes. The tumor suppressor gene TP53, which is defective in many types of cancer, was already known to accumulate many deletions in these sequences, known as 5′ untranslated regions. The MIT team found the same pattern in a tumor suppressor called ELF3.

The researchers also used their model to investigate whether common mutations that were already known might also be driving different types of cancers. As one example, the researchers found that BRAF, previously linked to melanoma, also contributes to cancer progression in smaller percentages of other types of cancers, including pancreatic, liver, and gastroesophageal.

“That says that there’s actually a lot of overlap between the landscape of common drivers and the landscape of rare drivers. That provides opportunity for therapeutic repurposing,” Sherman says. “These results could help guide the clinical trials that we should be setting up to expand these drugs from just being approved in one cancer, to being approved in many cancers and being able to help more patients.”

The research was funded, in part, by the National Institutes of Health and the National Cancer Institute.

To address this, researchers at University of California San Diego School of Medicine conducted a randomized clinical trial comparing the leading treatment program, Family-Based Treatment (FBT), with a new Guided Self-Help (GSH) program designed to provide similar resources in a less intensive and more accessible way.

The study, publishing June 17, 2022 in Pediatrics, found that GSH and FBT were similarly effective in supporting pediatric weight loss, but families were more likely to maintain attendance in GSH.

In the clinical trial, 164 children and their parents were randomly assigned to one of the two programs. Participants were recruited from two clinic sites in San Diego County, which primarily serve Latino families. The prevalence of childhood obesity in these neighborhoods (Escondido and Chula Vista) is 38 percent.

The traditional FBT program consists of 20 one-hour group sessions over six months. FBT is held at academic research centers, which adds geographical constraints. Attrition rates in these programs are high, with many parents noting scheduling issues, transportation difficulties and competing work and family responsibilities as contributing factors.

In response to these challenges, the GSH model was developed to provide shorter treatment sessions and greater scheduling flexibility. The new program consists of 14 visits, each 20 minutes in length and held at the child’s primary care clinic. Families are given material to practice between sessions in a self-directed manner, and then meet individually with a health coach to review and troubleshoot strategies.

Both programs teach families how to self-monitor food intake, set healthy goals and modify the home environment to promote behavioral change. Additional sessions address topics of body image, bullying and emotional health.

“The program is not framed around weight loss per se, but about developing healthy lifestyle behaviors,” said the study’s corresponding author Kyung E. Rhee, MD, professor of pediatrics at UC San Diego School of Medicine.

Nevertheless, children in both groups showed significant reductions in their body mass index percentiles, which were largely maintained at the time of the six-month follow-up. However, families assigned to GSH showed a nearly 70 percent lower risk of attrition, and reported greater satisfaction and convenience. GSH participants attended more than half of the treatment sessions while FBT participants only attended one in five sessions on average.

“The success of the Guided Self-Help program is really promising for both patients and physicians,” said Rhee. “It’s always rewarding to hear that families were so appreciative of our help, but we were also surprised by how grateful the physicians were to have this program available in their office. These can be difficult conversations for them to initiate during standard checkups, but knowing they had a clear and effective way to provide care was really empowering for them.”

In the current program, GSH health coaches were trained and employed by the research team. To sustain the program, Rhee said health care groups will have to work within the current primary care system to identify individuals who can provide these services on location. The goal, she said, is to work toward a collaborative care model in which clinics employ their own behavioral counselors and support the delivery of additional services at schools and community centers.

“We cannot make a difference if the families can’t show up for treatment,” said Rhee, “so we owe it to them to make these programs as accessible and effective as possible.”

Co-authors include: Lourdes Herrera, David Strong, Eastern Kang-Sim, Yuyan Shi and Kerri N. Boutelle, all at UC San Diego.

The Gaia space mission of the European Space Agency ESA is constructing an ultraprecise three-dimensional map of our Milky Way galaxy, observing almost two billion stars or roughly one percent of all the stars in our galaxy. Gaia was launched in December 2013 and has collected science data from July 2014. On Monday, June 13, ESA released Gaia data in Data Release 3 (DR3). Finnish researchers were strongly involved in the release.

Gaia data allows, for example, for the derivation of asteroid and exoplanet orbits and physical properties. The data helps unveil the origin and future evolution of the Solar System and the Milky Way and helps understand stellar and planetary-system evolution and our place in the cosmos.

Gaia revolves about its axis slowly in about six hours and is composed of two optical space telescopes. Three science instruments allow for accurate determination of stellar positions and velocities as well as the spectral properties. Gaia resides at about 1,5 million kilometers from the Earth in the anti-Sun direction, where it orbits the Sun together with the Earth in the proximity of the so-called Sun-Earth Lagrange L2-point.

Gaia DR3 on June 13, 2022 was significant across astronomy. Some 50 scientific articles are being published with DR3, of which nine articles have been devoted to underscoring the exceptionally significant potential of DR3 for future research.

The new DR3 data comprises, for example, the chemical compositions, temperatures, colors, masses, brightnesses, ages, and radial velocities of stars. DR3 includes the largest ever binary star catalog for the Milky Way, more than 150 000 Solar System objects, largely asteroids but also planetary satellites, as well as millions of galaxies and quasars beyond the Milky Way.

“There are so many revolutionary advances that it is difficult to pinpoint a single most significant advance. Based on Gaia DR3, Finnish researchers will change the conception of asteroids in our Solar System, exoplanets and stars in our Milky Way galaxy, as well as galaxies themselves, including the Milky Way and its surrounding satellite galaxies. Returning to our home planet, Gaia will produce an ultraprecise reference frame for navigation and positioning,” says Academy Professor Karri Muinonen from the University of Helsinki.

Gaia and asteroids

The ten-fold increase in the number of asteroids reported in Gaia DR3 as compared to DR2 means that there is a significant increase in the number of close encounters between Gaia-detected asteroids. These close encounters can be utilized for asteroid mass estimation and we expect a significant increase in the number of asteroid masses to be derived by using Gaia DR3 astrometry, in particular, when combined with astrometry obtained by other telescopes.

In the conventional computation of an asteroid’s orbit, the asteroid is assumed to be a point-like object and its size, shape, rotation and surface light scattering properties are not taken into account. The Gaia DR3 astrometry is, however, so accurate that the angular offset between the asteroid’s center of mass and the center of the area illuminated by the Sun and visible to Gaia must be accounted for. Based on Gaia DR3, the offset has been certified for asteroid (21) Lutetia (Figure 2). The ESA Rosetta space mission imaged Lutetia during the flyby on July 10, 2010. With the help of the Rosetta Lutetia imagery and ground-based astronomical observations, a rotation period, rotational pole orientation, and detailed shape model were derived. When the physical modeling is incorporated into orbit computation, the systematic errors are removed and, contrary to conventional computation, all observations can be incorporated into the orbit solution. Consequently, the Gaia astrometry provides information about the physical properties of asteroids. These properties need to be taken into account using physical models or empirical error models for the astrometry.

The Gaia DR3 includes, for the first time, spectral observations. The spectrum measures the color of the target, meaning the brightness at different wavelengths. One especially interesting feature is that the new release contains about 60 000 spectra of asteroids in our Solar System (Figure 3). The asteroid spectrum contains information on their composition and, thus, about their origin and the evolution of the whole Solar System. Before the Gaia DR3, there has been only few thousand asteroid spectra available, so Gaia will multiply the amount of data by more than an order of magnitude.

Gaia and exoplanets

Gaia is expected to produce detections of up to 20 000 giant exoplanets by measuring their gravitational effect on the movement of their host stars. This will enable finding virtually all Jupiter-like exoplanets in the Solar neighbourhood over the coming years and determining how common are Solar System -like architectures. The first such astrometric Gaia detection was a giant exoplanet around epsilon Indi A, that corresponds to the nearest Jupiter-like exoplanet only 12 light years away. The first such detections are possible because acceleration observed in radial velocity surveys can be combined with movement data from Gaia to determine the orbits and planetary masses.

Gaia and galaxies

The microarcsecond resolution of Gaia DR3 provides precise measurements of the motions of stars, not only within our own Milky Way galaxy, but also for the many satellite galaxies that surround it. From the motion of stars within the Milky Way itself, we can accurately measure its mass, and together with the proper motion of satellites, we can now accurately determine their orbits. This lets us look both into the past and into the future of the Milky Way galaxy system. For example, we can find out which of the galaxies that surround the Milky Way are true satellites, and which are just passing by. We can also investigate if the evolution of the Milky Way conforms to cosmological models, and in particular, whether the satellite orbits fit the standard dark matter model.

Gaia and reference frames

The International Celestial Reference Frame, ICRF3, is based on the position of a few thousand quasars determined by Very Long Baseline Interferometry (VLBI) at radio wavelengths. ICRF3 is used to obtain the coordinates of celestial objects and to determine the orbits of satellites. Quasars of ICRF3 are also fixed points on the sky that can be used to determine the precise orientation of the Earth in space at any time. Without this information, for example, satellite positioning would not work.

Gaia’s data contain about 1,6 million quasars, which can be used to create a more accurate Celestial Reference Frame in visible light replacing the current one. In the future, this will have an impact on the accuracy of both satellite positioning and measurements of Earth-exploring satellites.

Biologists from the University of Cincinnati are retracing two exhaustive surveys conducted 100 years apart to see how the Queen City’s plant diversity has changed over the past two centuries. They focused their attention on undeveloped parts of cemeteries, banks of the Mill Creek and public parks that have remained protected from development during the last 200 years.

The study, titled “The rise of nonnative plants in wooded natural areas in southwestern Ohio,” was published in June in the journal Ecological Restoration.

UC’s latest survey follows in the footsteps of Cincinnati botanist Thomas G. Lea, who conducted a plant survey in Cincinnati between 1834 and 1844. During that time, he built up an herbarium of specimens that went to the Academy of Natural Sciences in Philadelphia. Lea identified some 714 species before he died in 1844. His work was published posthumously in 1849 by his brother.

A century later, famed UC botanist E. Lucy Braun retraced Lea’s path, conducting a second plant survey in Cincinnati that found more than 1,400 species in her 1934 study published in The American Midland Naturalist. She leaned on Lea’s meticulous notes to return to the places he visited, many of which had been developed into homes, roads or apartment buildings over the decades.

UC biologist Denis Conover and his co-author Robert Bergstein retraced the steps of Braun and Lea in southwest Ohio in places where city development did not pave over natural areas. They found that many species purposely introduced as landscaping plants are flourishing in the wild.

“The spread of nonnative invasive species into wooded natural areas in southwestern Ohio threatens the continued survival of native flora and fauna. Efforts by park managers and volunteers to control invasive plant species has become a major part of their duties. This effort will be required in perpetuity and will be at great expense both monetarily and timewise due to collateral damage to native plants, wildlife and humans caused by the extensive use of herbicides, chainsaws and other mechanical equipment,” the study concluded.

Horticulturists introduced most of the nonnative plants from Europe and Asia as ornamentals. Their seeds eventually spread in the wild.

The biggest culprit? Amur honeysuckle, a woody shrub that has taken over many eastern forests.

“It has escaped into the wild and is propagating on its own,” said Conover, a professor of biology in UC’s College of Arts and Sciences.

Not to be confused with native trumpet honeysuckle, which grows in southern states and is referenced in the works of American writers William Faulkner and Robert Frost, Amur honeysuckle is a shrub from Asia that has delicate white flowers in the spring and red berries in the fall.

“Amur honeysuckle is now the most abundant woody plant in Hamilton County,” he said. “One bush can produce thousands of seeds that get dispersed by birds and mammals.”

A survey by Braun in 1961 found Amur honeysuckle starting to grow in some parts of Hamilton County but not yet spreading in the wild in other Ohio counties. Today, it is a dominant woody plant found ubiquitously throughout the state, crowding out virtually all other low-lying vegetation, the study found.

“In some woodlands, the Amur honeysuckle layer is so dense that the only native species remaining are older trees whose canopy is already growing above the shrub layer,” the study said.

“It leafs out before native woody plants and holds its leaves longer into the fall,” Conover said.

Some invasive plants are successful because they produce chemicals that hinder the growth or germination of nearby competitors, an insidious weapon called allelopathy, he said.

Conover said where these introduced plants are found, there is often far less biodiversity to support wildlife and the food chain. Once they take hold, eradicating plants like Amur honeysuckle is labor-intensive, expensive and time consuming.

“Native plants just don’t have a chance. Everything that depends on the native plants — insects, birds — can be lost,” Conover said. “When they introduce nonnative plants to the United States, they can also import fungal diseases that can wipe out native trees, which is what happened with the American chestnut.”

Callery pear trees with their pretty spring flowers and quick growing times were a favorite tree to plant in front yards of new subdivisions. Today, they grow wild along highways and forests.

Ohio lawmakers plan to phase in a ban on the sale of Callery pear trees in 2023.

The UC survey found dozens of other examples of foreign species that have taken root in southwest Ohio’s woods, including porcelain berry, tree of heaven, winged euonymus, European buckthorn, Oriental bittersweet, common privet and lesser periwinkle. It also found Norway maple, Amur cork tree and white poplar along with herbaceous species such as lesser celandine, garlic mustard, Japanese knotweed and Japanese stilt grass.

Every year in the United States, nearly two million Americans sustain a traumatic brain injury (TBI). Survivors can live with lifelong physical, cognitive and emotional disabilities. Currently, there are no treatments.

One of the biggest challenges for neuroscientists has been to fully understand how a TBI alters the cross-talk between different cells and brain regions.

In the new study, researchers improved upon a process called iDISCO, which uses solvents to make biological samples transparent. The process leaves behind a fully intact brain that can be illuminated with lasers and imaged in 3D with specialized microscopes.

With the enhanced brain clearing processes, the UCI team mapped neural connections throughout the entire brain. The researchers focused on connections to inhibitory neurons, because these neurons are extremely vulnerable to dying after a brain injury. The team first looked at the hippocampus, a brain region responsible for learning and memory. Then, they investigated the prefrontal cortex, a brain region that works together with hippocampus. In both cases, the imaging showed that inhibitory neurons gain many more connections from neighboring nerve cells after TBI, but they become disconnected from the rest of the brain.

“We’ve known for a long time that the communication between different brain cells can change very dramatically after an injury,” said Robert Hunt, PhD, associate professor of anatomy and neurobiology and director of the Epilepsy Research Center at UCI School of Medicine whose lab conducted the study, “But, we haven’t been able to see what happens in the whole brain until now.”

To get a closer look at the damaged brain connections, Hunt and his team devised a technique for reversing the clearing procedure and probing the brain with traditional anatomical approaches.

The findings surprisingly showed that the long projections of distant nerve cells were still present in the damaged brain, but they no longer formed connections with inhibitory neurons.

“It looks like the entire brain is being carefully rewired to accommodate for the damage, regardless of whether there was direct injury to the region or not,” explained Alexa Tierno, a graduate student and co-first author of the study. “But different parts of the brain probably aren’t working together quite as well as they did before the injury.”

The researchers then wanted to determine if it was possible for inhibitory neurons to be reconnected with distant brain regions. To find out, Hunt and his team transplanted new interneurons into the damaged hippocampus and mapped their connections, based on the team’s earlier research demonstrating interneuron transplantation can improve memory and stop seizures in mice with TBI.

The new neurons received appropriate connections from all over the brain. While this may mean it could be possible to entice the injured brain to repair these lost connections on its own, Hunt said learning how transplanted interneurons integrate into damaged brain circuits is essential for any future attempt to use these cells for brain repair.

“Our study is a very important addition to our understanding of how inhibitory progenitors can one day be used therapeutically for the treatment of TBI, epilepsy or other brain disorders,” said Hunt. “Some people have proposed interneuron transplantation might rejuvenate the brain by releasing unknown substances to boost innate regenerative capacity, but we’re finding the new neurons are really being hard wired into the brain.”

Hunt hopes to eventually develop cell therapy for people with TBI and epilepsy. The UCI team is now repeating the experiments using inhibitory neurons produced from human stem cells.

“This work takes us one step closer to a future cell-based therapy for people,” Hunt said, “Understanding the kinds of plasticity that exists after an injury will help us rebuild the injured brain with a very high degree of precision. However, it is very important that we proceed step wise toward this goal, and that takes time.”

Jan C. Frankowski, PhD; Shreya Pavani; Quincy Cao and David C. Lyon, PhD also contributed to this study. Funding was provided by the National Institutes of Health.