Turning brain cells on using the power of light

 University of Rochester researchers have demonstrated a noninvasive method using BL-OG, or bioluminescent optogenetics, that harnesses light to activate neurons in the brain. The ability to regulate brain activation could transform invasive procedures such as deep brain stimulation that are used to treat Parkinson's disease and other neurological conditions.

The advantage of this new technique is that it can create brain activation without the use of an implanted device in the brain to deliver physical light, according to Manuel Gomez-Ramirez, an assistant professor of brain and cognitive sciences and with the University's Del Monte Institute for Neuroscience, and the senior author of the study, which appears in the journal NeuroImage

"BL-OG is an ideal method for noninvasively teasing apart neural circuits in the brain," says Emily Murphy, the first author of the study and manager of the Haptics Lab, led by Gomez-Ramirez. "There are still so many things to learn about the structure and function of distinct brain areas and neuronal cell types that will help us understand how healthy brains function."

How to turn on a light -- without a switch

To turn on light in the brain, researchers need a few tools. The first one is optogenetics, an established research technique that uses light to activate or inactivate cells in the brain. The next tool is bioluminescence, the same chemical reaction that gives a firefly its glow, which provides the light optogenetics needs to work.

Combining these tools creates the material needed for BL-OG. But in order to work, BL-OG still needs something to "turn on" the light. The organic substance luciferin, when combined with bioluminescence, creates light that activates the optogenetics and modulates cellular response in the brain without an incision. Previous work by Gomez-Ramirez has shown that the chemical luciferin is harmless to the body.

The researchers in the Haptics Lab tested this combination. They put BL-OG into a pre-determined brain region in mice. They then injected luciferin through a vein in the animal's tail to activate the targeted cells in the brain. They found that BL-OG effects occur rapidly in the brain, but that these effects could be controlled by scaling the dosage of the luciferin in the animal.

'Fine-tuning' bioluminescent optogenetics

"The advantage of this technique is we can create brain activation without a cable. There is less risk for infection and other things to go awry because it is a noninvasive method," Gomez-Ramirez says. "If we want to standardize this technique in the lab, and potentially in the clinic, it is critical to map all the important parameters around using it. These latest findings allow us to now work on fine-tuning the desired effects of BL-OG based on need and requirements."

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Neuroscientists spark shelter-seeking response by reactivating memory circuit

 Using a sophisticated brain-imaging system, neuroscientists at Johns Hopkins Medicine say they have successfully reactivated a specific memory circuit in mice, causing them to seek out shelter when no shelter is actually present.

The researchers say the study, published Sept. 27 in Nature Neuroscience, advances understanding of how memories are structured in the mammalian brain. The findings could one day point to new ways of slowing down or preventing the memory loss that accompanies Alzheimer's and other neurodegenerative diseases.

Specifically, the team found that stimulating neurons in two areas of mouse brains -- the nucleus accumbens, also known as the brain's "pleasure center" responsible for relaying dopamine-dependent behaviors, and the dorsal periaqueductal gray (dPAG), responsible for defensive behavior -- reactivated a "spatial memory" and caused the mice to seek shelter.

"When we artificially reactivate those memory circuits in the brain, it triggers the mouse to do the same thing it did naturally, even without the fear stimuli that cause them to seek shelter to begin with," says senior author Hyungbae Kwon, Ph.D., associate professor of neuroscience at the Johns Hopkins University School of Medicine.

The scientists say they aimed to map out which areas of the brain are responsible for navigating one's surroundings, a high-level cognitive function among mammals, including humans. Thus, these experiments, which tested whether such cognitive brain functions can be replayed randomly, may have applications in understanding how other mammals behave, perceive and sense their environment.

In the new experiments, the researchers first allowed laboratory mice to explore their surroundings in a box with a shelter in the corner. The team placed a series of visual cues, including triangles, circles and stripes in different colors, to help the mice locate the shelter based on nearby landmarks. The mice acclimated to the area for seven minutes, entering and exiting the shelter.

Then, the researchers added a visual or auditory looming signal to spur them to seek shelter -- also forming a spatial memory relative to their location and the visual cues.

To selectively tag shelter memory neurons, the researchers used a light-activated gene-expression switching system called Cal-light, which Kwon developed in 2017. Once the scientists identified these neurons in the nucleus accumbens, they switched on expression of the genes associated with them, reactivating the shelter-seeking memory in mice while also activating neurons in the dPAG.

In turn, the mice sought out the area of the box where the shelter had once been, when neither the original threat nor the shelter were present.

To get to this point, the researchers first selectively activated neurons in the nucleus accumbens and then, separately, in the dPAG, to see whether switching on neurons in just one area of the brain would cause this behavior.

"Surprisingly, we found that the mice did not seek out shelter when we activated neurons in the nucleus accumbens alone," Kwon says. "Whereas switching on neurons in the dPAG caused the mice to react randomly, but did not guide them specifically to the area where they sought shelter before."

"The Cal-light system allowed us to selectively tag a specific function in the brain, helping us to map out memory on a cellular level," says Kwon.

Eventually, Kwon says this research could provide a foundation for reactivating or engineering memory circuits in people with Alzheimer's.

"If we understand the macro-level structure of memory, then we may be able to develop more effective strategies to prevent or slow down neurodegenerative diseases using this method," he says.

The researchers say they hope to understand brain-wide memory structure by selectively tagging and reactivating neurons with different functions in different areas of the brain that lead to other specific behaviors.

"Understanding how all of these memory circuits work together will help us understand brain function better," he says.

Other researchers involved in the study are Kanghoon Jung, Sarah Krüssel, Sooyeon Yoo, Benjamin Burke, Nicholas Schappaugh, Youngjin Choi and Seth Blackshaw of Johns Hopkins; Myungmo An of the Max Planck Florida Institute for Neuroscience; and Zirong Gu and Rui M. Costa of the Zuckerman Mind Brain Behavior Institute at Columbia University and the Allen Institute.

Funding for this work was provided by the Max Planck Florida Institute for Neuroscience, a National Alliance for Research on Schizophrenia and Depression Young Investigator Grant and National Institutes of Health Grants R01MH107460, 5U19NS104649, K99 NS119788, DK108230 and DP1MH119428.

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Study of monkey fossils found in cave sheds light on the animals' extinction centuries ago

 By studying rare fossils of jaws and other skull parts of a long-extinct Caribbean monkey, a team of researchers that includes a Johns Hopkins University School of Medicine professor says it has uncovered new evidence documenting the anatomy and ecology of an extinct primate once found on Hispaniola -- the Caribbean island on which Haiti and the Dominican Republic are located.

The fossils were found in flooded caves in the Dominican Republic. The cache, including seven skulls, five mandibles (jawbones) and dozens of other skeleton parts, makes the fossil site, Cueva Macho, the richest one yet for primate fossils on Hispaniola, the researchers say.

The research was published Sept. 30 in the Journal of Human Evolution.

Evidence indicates that the monkey, Antillothrix bernensis, became extinct sometime during the last 10,000 years, says senior author Siobhán Cooke, Ph.D., associate professor of functional anatomy and evolution at the Johns Hopkins University School of Medicine.

"These fossils help us to better understand the anatomy of Antillothrix, which can help us identify ecological factors that might have predisposed it to extinction," Cooke says. "These data can ultimately guide policy for preserving the remaining mammalian diversity on the Caribbean islands and elsewhere."

Cooke was part of the team that identified the first skull of a juvenile Hispaniolan monkey from a flooded cave in the Dominican Republic in 2009. Since then, divers from the Dominican Republic Speleological Society, in collaboration with Juan Almonte-Milán, curator at the Museo Nacional de Historia Natural "Prof. Eugenio de Jesús Marcano," continued to search similar wet caves nearby, leading to discovery of the most recent set of fossils in 2018.

The opportunity to study this many fossils of South American and Caribbean monkeys is rare, Cooke says. Only one other species of extinct South American monkey, Homunculus patagonicus (a long extinct animal lived in Patagonia), is known for a comparably large sample of fossils.

"The number and quality of the Antillothrix crania outlined in this paper allow us to describe the skull completely and understand variation between individuals," Cooke says. "This can tell us about the diet and social systems of these animals."

Using virtual three-dimensional models the researchers made of the fossils, which are housed in the National Museum of Natural History in Santo Domingo, Dominican Republic, scientists concluded that male and female Hispaniola monkeys were monomorphic (they were about the same size as one another) and weighed up to five pounds.

"This indicates that there was little competition for mates among males," says Cooke. "They may have lived in small family groups consisting of a female, male and dependent offspring."Looking at the fossils' rounded teeth and relatively small canines, researchers also say the extinct monkeys' diet consisted mainly of fruit.

Antillothrix may have a modern relative. At just over two pounds, the South American Titi monkey, with its short canine teeth, offers the closest glimpse at what the Hispaniola monkey may have looked like in the wild.

But how did seven or eight Hispaniola monkeys end up at the bottom of a cave approximately 10,000 years ago?

Cooke says it could be a matter of bad luck -- though it seems unlikely that up to eight tree-dwelling primates would fall into a cave.

Evidence of injuries in the monkeys' jaw fossils provided the researchers with another potential answer: an owl predator.

One Antillothrix skull includes only the front teeth, but not the ramus, or the back portion of the jaw. Other skulls are missing small pieces or large chunks of their jaws.

"When owls feed, they will sometimes preferentially consume the masseter, a major muscle attached to the jaw, and these injuries are consistent with that," Cooke says. "It could be possible that a now extinct owl, which would have been quite large, caught these monkeys and brought them into the cave where it was living -- rather than the monkeys falling in at random. Owl feeding deposits are not uncommon in Hispaniolan caves."

The researchers next intend to take a closer look at other Antillothrix bones, including limb bones, ribs and vertebrae.

"Learning more about these animals provides a window into the past and helps us better appreciate the current and past biological diversity of the Dominican Republic and Haiti," Cooke says.

She notes that these countries once had not only monkeys and giant owls but also giant sloths, large rodents and several species of insect-eating shrews, crocodiles and tortoises.In addition to Cooke and Milán, other researchers involved in the study are first author Lauren Halenar-Price of Farmingdale State College, Zachary Klukkert of Oklahoma State University, Phillip Lehman of the Dominican Republic Speleological Society and Zana Sims, a postdoctoral fellow at the University of Southern California who conducted work on this study as a Johns Hopkins doctoral student.

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The true global impact of species-loss caused by humans is far greater than expected

 The extinction of hundreds of bird species caused by humans over the last 130,000 years has has led to substantial reductions in avian functional diversity -- a measure of the range of different roles and functions that birds undertake within the environment -

and resulted in the loss of approximately 3 billion years of unique evolutionary history, according to a new study published today in Science.

Whilst humans have been driving a global erosion of species richness for millennia, the consequences of past extinctions for other dimensions of biodiversity are poorly known. New research lead by the University of Birmingham highlights the severe consequences of the ongoing biodiversity crisis and the urgent need to identify the ecological functions being lost through extinction.

From the well-documented Dodo to the recent Kauaʻi ʻōʻō songbird declared extinct in 2023, scientists currently have evidence of at least 600 bird species having become extinct as a result of humans since the Late Pleistocene when modern humans started to spread throughout the world. Using the most comprehensive dataset to date of all known bird extinctions during the Late Pleistocene and Holocene, the paper 'The global loss of avian functional and phylogenetic diversity from anthropogenic extinctions' looks beyond the number of extinctions to the wider implications on the planet.

Lead author Dr Tom Matthews from the University of Birmingham explained: "The sheer number of bird species that have become extinct is of course a big part of the extinction crisis but what we also need to focus on is that every species has a job or function within the environment and therefore plays a really important role in its ecosystem. Some birds control pests by eating insects, scavenger birds recycle dead matter, others eat fruit and disperse the seeds enabling more plants and trees to grow, and some, like hummingbirds, are very important pollinators. When those species die out, the important role that they play (the functional diversity) dies with them.

"In addition to functional diversity each species also carries a certain amount of evolutionary history, therefore when that species becomes extinct, it's basically like chopping off a branch of the tree of life and all of that associated phylogenetic diversity is also lost."

The research found that the scale of anthropologenic bird extinctions to date has resulted in a loss of approximately 3 billion years of unique evolutionary history, and 7% of global avian functional diversity -- a significantly larger amount than expected based on the number of extinctions. Given the wide range of important ecological roles performed by birds, the loss of avian functional diversity in particular will likely have had far-reaching implications. These post-extinction aftershocks include reduced flower pollination, reduced seed dispersal, the breakdown of top-down control of insect populations -- including many pests and disease vectors -- as well as increased disease outbreaks due to reduced consumption of carrion. In addition, the downsizing of the global avifauna documented in the research will likely affect the ability of many plant species to track present and future climate change.

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Ant agriculture began 66 million years ago in the aftermath of the asteroid that doomed the dinosaurs

 When humans began farming crops thousands of years ago, agriculture had already been around for millions of years. In fact, several animal lineages have been growing their own food since long before humans evolved as a species.

According to a new study, colonies of ants began farming fungi when an asteroid struck Earth 66 million years ago. This impact caused a global mass extinction but also created ideal conditions for fungi to thrive. Innovative ants began cultivating the fungi, creating an evolutionary partnership that became even more tightly intertwined 27 million years ago and continues to this day.In a paper published today, Oct. 3, in the journal Science, scientists at the Smithsonian's National Museum of Natural History analyzed genetic data from hundreds of species of fungi and ants to craft detailed evolutionary trees. Comparing these trees allowed the researchers to create an evolutionary timeline of ant agriculture and pinpoint when ants first began cultivating fungi."Ants have been practicing agriculture and fungus farming for much longer than humans have existed," said entomologist Ted Schultz, the museum's curator of ants and the lead author of the new paper. "We could probably learn something from the agricultural success of these ants over the past 66 million years."Nearly 250 different species of ants in the Americas and Caribbean farm fungi. Researchers organize these ants into four agricultural systems based on their cultivation strategies. Leafcutter ants are among those that practice the most advanced strategy, known as higher agriculture. These ants harvest bits of fresh vegetation to provide sustenance for their fungi, which in turn grow food for the ants called gongylidia. This food helps fuel complex colonies of leaf cutter ants that can number in the millions.Schultz has spent 35 years studying the evolutionary relationship between ants and fungi. He has conducted more than 30 expeditions to locales in Central and South America to observe this interaction in the wild and has reared colonies of leafcutter and other fungus-farming ants in his lab at the museum. Over the years, Schultz and colleagues have collected thousands of genetic samples of ants and fungi from throughout the tropics.This stockpile of samples was crucial to the new paper."To really detect patterns and reconstruct how this association has evolved through time, you need lots of samples of ants and their fungal cultivars," Schultz said.The team used the samples to sequence genetic data for 475 different species of fungi (288 of which are cultivated by ants) and 276 different species of ants (208 of which cultivate fungi) -- the largest genetic dataset of fungus-farming ants ever assembled. This allowed the researchers to create evolutionary trees of the two groups. Comparing wild fungal species with their cultivated relatives helped the researchers determine when ants began utilizing certain fungi.

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2-billion-year-old rock home to living microbes

 Pockets of microbes have been found living within a sealed fracture in 2-billion-year-old rock. The rock was excavated from the Bushveld Igneous Complex in South Africa, an area known for its rich ore deposits. This is the oldest example of living microbes being found within ancient rock so far discovered. The team involved in the study built on its previous work to perfect a technique involving three types of imaging -- infrared spectroscopy, electron microscopy and fluorescent microscopy -- to confirm that the microbes were indigenous to the ancient core sample and not caused by contamination during the retrieval and study process. Research on these microbes could help us better understand the very early evolution of life, as well as the search for extraterrestrial life in similarly aged rock samples brought back from Mars.

Deep in the earth lies something ancient and alive. Colonies of microbes live in rocks far beneath the surface, somehow managing to survive for thousands, even millions of years. These tiny, resilient organisms appear to live life at a slower pace, scarcely evolving over geological time spans and so offering us a chance to peek back in time. Now, researchers have found living microbes in a rock sample dated to be 2 billion years old.

"We didn't know if 2-billion-year-old rocks were habitable. Until now, the oldest geological layer in which living microorganisms had been found was a 100-million-year-old deposit beneath the ocean floor, so this is a very exciting discovery. By studying the DNA and genomes of microbes like these, we may be able to understand the evolution of very early life on Earth,"said Yohey Suzuki, lead author and associate professor from the Graduate School of Science at the University of Tokyo.

The rock sample was taken from the Bushveld Igneous Complex (BIC), a rocky intrusion in northeastern South Africa which formed when magma slowly cooled below the Earth's surface. The BIC covers an area of approximately 66,000 square kilometers (roughly the size of Ireland), varies in thickness by up to 9 km, and contains some of the richest ore deposits on Earth including about 70% of the world's mined platinum.

Due to the way it was formed and minimal deformation or change occurring to it since then, the BIC is believed to have provided a stable habitat for ancient microbial life to continue until today.

With the aid of the International Continental Scientific Drilling Program, a nonprofit organization that funds exploration at geological sites, the team obtained a 30-centimeter-long rock core sample from about 15 meters belowground. The rock was cut into thin slices and analyzed, which is when the team discovered living microbial cells densely packed into cracks in the rock. Any gaps near these cracks were clogged with clay, making it impossible for the organisms to leave or for other things to enter.

The team built on a technique they had previously developed to confirm that the microbes were native to the rock sample, and not due to contamination during the drilling or examination process. By staining the DNA of the microbial cells and using infrared spectroscopy to look at the proteins in the microbes and surrounding clay, the researchers could confirm that the microorganisms were both alive and not contaminated.

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Pterosaurs needed feet on the ground to become giants

 The evolutionary adaptations that allowed ancient pterosaurs to grow to enormous sizes have been pinpointed for the first time by palaeontologists in the Centre for Palaeobiology and Biosphere Evolution at the University of Leicester.

The discovery revealed a surprising twist -- the ability to walk efficiently on the ground played a crucial role in determining how large the biggest flying animals could grow, with some reaching wingspans of up to 10 metres.

In a new study published in Current Biology, a team of researchers led by the University of Leicester examined the hands and feet of pterosaurs from around the world and across their entire evolutionary history.

They uncovered a surprising level of variation similar to that seen across living birds. This discovery indicates that pterosaurs were not confined to a life in the skies but were also adapted to a wide range of terrestrial lifestyles, from tree-climbing in early species to more ground-based lifestyles in later ones.

The evolution of pterosaurs, the first true flying vertebrates, showcases some of the most remarkable adaptations in the history of life. While these creatures are best known for their ability to soar through the prehistoric skies of the Mesozoic era (252-66 million years ago), a new study has revealed a surprisingly high degree of diversity in where and how pterosaurs lived when they were not airborne.

Lead author Robert Smyth, a doctoral researcher in the in the Centre for Palaeobiology and Biosphere Evolution (School of Geography, Geology and the Environment at the University of Leicester), explained: "Early pterosaurs were highly specialised for climbing, with extreme modifications in their hands and feet, similar to those found in climbing lizards and birds like woodpeckers today. Clinging to vertical surfaces by your fingertips for long periods is hard work -- it's a lot easier for small, lightweight animals."

These early pterosaurs were likely restricted to arboreal habitats and consequently, small body sizes. However, a major evolutionary shift occurred during the Middle Jurassic period, when pterosaur hands and feet changed to look much more like those of ground-dwelling animals. These adaptations to ground-based movement opened up new ecological opportunities, leading to a wide variety of feeding strategies. Freedom from the size constraints imposed by vertical living allowed some pterosaurs to evolve to gigantic size with wingspans of up to 10 metres.

Co-author Dr David Unwin from the University of Leicester added: "In early pterosaurs the hind limbs were connected by a flight membrane which severely impeded walking and running. In later, more advanced pterosaurs, this membrane became separated along the midline, allowing each hind limb to move independently. This was a key innovation that, combined with changes to their hands and feet, greatly improved pterosaurs' mobility on the ground.

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