Scientists monitor brains replaying memories in real time

Brain abstract illustration (stock image).

In a study of epilepsy patients, researchers at the National Institutes of Health monitored the electrical activity of thousands of individual brain cells, called neurons, as patients took memory tests. They found that the firing patterns of the cells that occurred when patients learned a word pair were replayed fractions of a second before they successfully remembered the pair. The study was part of an NIH Clinical Center trial for patients with drug-resistant epilepsy whose seizures cannot be controlled with drugs.

"Memory plays a crucial role in our lives. Just as musical notes are recorded as grooves on a record, it appears that our brains store memories in neural firing patterns that can be replayed over and over again," said Kareem Zaghloul, M.D., Ph.D., a neurosurgeon-researcher at the NIH's National Institute of Neurological Disorders and Stroke (NINDS) and senior author of the study published in Science.

Dr. Zaghloul's team has been recording electrical currents of drug-resistant epilepsy patients temporarily living with surgically implanted electrodes designed to monitor brain activity in the hopes of identifying the source of a patient's seizures. This period also provides an opportunity to study neural activity during memory. In this study, his team examined the activity used to store memories of our past experiences, which scientists call episodic memories.

In 1957, the case of an epilepsy patient H.M. provided a breakthrough in memory research. H.M could not remember new experiences after part of his brain was surgically removed to stop his seizures. Since then, research has pointed to the idea that episodic memories are stored, or encoded, as neural activity patterns that our brains replay when triggered by such things as the whiff of a familiar scent or the riff of a catchy tune. But exactly how this happens was unknown.

Over the past two decades, rodent studies have suggested that the brain may store memories in unique neuronal firing sequences. After joining Dr. Zaghloul's lab, Alex P. Vaz, B.S., an M.D., Ph.D. student at Duke University, Durham, North Carolina, and the leader of this study decided to test this idea in humans.

"We thought that if we looked carefully at the data we had been collecting from patients we might be able to find a link between memory and neuronal firing patterns in humans that is similar to that seen in rodents," said Vaz, a bioengineer who specializes in deciphering the meaning of electrical signals generated by the body.

To do this they analyzed the firing patterns of individual neurons located in the anterior temporal lobe, a brain language center. Currents were recorded as patients sat in front of a screen and were asked to learn word pairs such as "cake" and "fox." The researchers discovered that unique firing patterns of individual neurons were associated with learning each new word pattern. Later, when a patient was shown one of the words, such as "cake," a very similar firing pattern was replayed just milliseconds before the patient correctly recalled the paired word "fox."

"These results suggest that our brains may use distinct sequences of neural spiking activity to store memories and then replay them when we remember a past experience," said Dr. Zaghloul.

Last year, his team showed that electrical waves, called ripples, may emerge in the brain just split seconds before we remember something correctly. In this study, the team discovered a link between the ripples recorded in the anterior temporal lobe and the spiking patterns seen during learning and memory. They also showed that ripples recorded in another area called the medial temporal lobe slightly preceded the replay of firing patterns seen in the anterior temporal lobe during learning.

"Our results support the idea that memories involve coordinated replay of neuronal firing patterns throughout the brain," said Dr. Zaghloul. "Studying how we form and retrieve memories may not only help us understand ourselves but also how neuronal circuits break down in memory disorders."

This study was supported by the NINDS Intramural Research Program and NIH training grants (NS113400, GM007171).

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Materials provided by NIH/National Institute of Neurological Disorders and Stroke. Note: Content may be edited for style and length.

Scientists unravel mystery of photosynthesis

Sunlight and leaves (stock image).

Plants have been harnessing the sun's energy for hundreds of millions of years.

Algae and photosynthetic bacteria have been doing the same for even longer, all with remarkable efficiency and resiliency.

It's no wonder, then, that scientists have long sought to understand exactly how they do this, hoping to use this knowledge to improve human-made devices such as solar panels and sensors.

Scientists from the U.S. Department of Energy's (DOE) Argonne National Laboratory, working closely with collaborators at Washington University in St. Louis, recently solved a critical part of this age-old mystery, homing in on the initial, ultrafast events through which photosynthetic proteins capture light and use it to initiate a series of electron transfer reactions.

"In order to understand how biology fuels all of its engrained activities, you must understand electron transfer," said Argonne biophysicist Philip Laible. "The movement of electrons is crucial: it's how work is accomplished inside a cell."

In photosynthetic organisms, these processes begin with the absorption of a photon of light by pigments localized in proteins.

Each photon propels an electron across a membrane located inside specialized compartments within the cell.

"The separation of charge across a membrane -- and stabilization of it -- is critical as it generates energy that fuels cell growth," said Argonne biochemist Deborah Hanson.

The Argonne and Washington University research team has gained valuable insight on the initial steps in this process: the electron's journey.

Nearly 35 years ago, when the first structure of these types of complexes was unveiled, scientists were surprised to discover that after the absorption of light, the electron transfer processes faced a dilemma: there are two possible pathways for the electron to travel.

In nature, plants, algae and photosynthetic bacteria use just one of them -- and scientists had no idea why.

What they did know was that the propulsion of the electron across the membrane -- effectively harvesting the energy of the photon -- required multiple steps.

Argonne and Washington University scientists have managed to interfere with each one of them to change the electron's trajectory.

"We've been on this trail for more than three decades, and it is a great accomplishment that opens up many opportunities," said Dewey Holten, a chemist at Washington University.

The scientists' recent article, "Switching sides -- Reengineered primary charge separation in the bacterial photosynthetic reaction center," published in the Proceedings of the National Academy of Sciences, shows how they discovered an engineered version of this protein complex that switched the utilization of the pathways, enabling the one that was inactive while disabling the other.

"It is remarkable that we have managed to switch the direction of initial electron transfer," said Christine Kirmaier, Washington University chemist and project leader. "In nature, the electron chose one path 100 percent of the time. But through our efforts, we have been able to make the electron switch to an alternate path 90 percent of the time. These discoveries pose exciting questions for future research."

As a result of their efforts, the scientists are now closer than ever to being able to design electron transfer systems in which they can send an electron down a pathway of their choosing.

"This is important because we are gaining the ability to harness the flow of energy to understand design principles that will lead to new applications of abiotic systems," Laible said. "This would allow us to greatly improve the efficiency of many solar-powered devices, potentially making them far smaller. We have a tremendous opportunity here to open up completely new disciplines of light-driven biochemical reactions, ones that haven't been envisioned by nature. If we can do that, that's huge."

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Materials provided by DOE/Argonne National Laboratory. Original written by Jo Napolitano. Note: Content may be edited for style and length.

Scientists find record warm water in Antarctica, pointing to cause behind troubling glacier melt

Antarctica illustration (stock image).

A team of scientists has observed, for the first time, the presence of warm water at a vital point underneath a glacier in Antarctica -- an alarming discovery that points to the cause behind the gradual melting of this ice shelf while also raising concerns about sea-level rise around the globe.

"Warm waters in this part of the world, as remote as they may seem, should serve as a warning to all of us about the potential dire changes to the planet brought about by climate change," explains David Holland, director of New York University's Environmental Fluid Dynamics Laboratory and NYU Abu Dhabi's Center for Global Sea Level Change, which conducted the research. "If these waters are causing glacier melt in Antarctica, resulting changes in sea level would be felt in more inhabited parts of the world."

The recorded warm waters -- more than two degrees above freezing -- flow beneath the Thwaites Glacier, which is part of the Western Antarctic Ice Sheet. The discovery was made at the glacier's grounding zone -- the place at which the ice transitions between resting fully on bedrock and floating on the ocean as an ice shelf and which is key to the overall rate of retreat of a glacier.

Thwaites' demise alone could have significant impact globally.

It would drain a mass of water that is roughly the size of Great Britain or the state of Florida and currently accounts for approximately 4 percent of global sea-level rise. Some scientists see Thwaites as the most vulnerable and most significant glacier in the world in terms of future global sea-level rise -- its collapse would raise global sea levels by nearly one meter, perhaps overwhelming existing populated areas.

While the glacier's recession has been observed over the past decade, the causes behind this change had previously not been determined.

"The fact that such warm water was just now recorded by our team along a section of Thwaites grounding zone where we have known the glacier is melting suggests that it may be undergoing an unstoppable retreat that has huge implications for global sea level rise," notes Holland, a professor at NYU's Courant Institute of Mathematical Sciences.

The scientists' measurements were made in early January, after the research team created a 600-meter deep and 35-centimeter wide access hole and deployed an ocean-sensing device to measure the waters moving below the glacier's surface. This device gauges the turbulence of the water as well as other properties such as temperature. The result of turbulence is the mixing of fresh meltwater from the glacier and salty water from the ocean.

It marks the first time that ocean activity beneath the Thwaites Glacier has been accessed through a bore hole and that a scientific instrument measuring underlying ocean turbulence and mixing has been deployed. The hole was opened on January 8 and 9 and the waters beneath the glacier measured January 10 and 11.

Aurora Basinski, an NYU graduate student who made the turbulence measurement, said, "From our observations into the ocean cavity at the grounding zone we observed not only the presence of warm water, but also its turbulence level and thus its efficiency to melt the ice shelf base."

Another researcher, Keith Nicholls, a scientist with the British Antarctic Survey, added, "This is an important result as this is the first time turbulent dissipation measurements have been made in the critical grounding zone of the West Antarctic Ice Sheet."

This research was supported by a $2.1 million, five-year grant from the National Science Foundation (PLR-1739003). The grant is part of the International Thwaites Glacier Collaboration (ITGC), headed by the United Kingdom's Natural Environment Research Council and the National Science Foundation, which has been deploying scientists to gather the data needed to understand whether the glacier's collapse could begin in the next few decades or centuries. Other members of the field team included researchers from Penn State, Georgia Tech, and the British Antarctic Survey.

For more about the project, please visit: https://thwaitesglacier.org/projects/melt

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Materials provided by New York University. Note: Content may be edited for style and length.

Scientists breach brain barriers to attack tumors

Illustration of human brain and tumor (stock image).

The brain is a sort of fortress, equipped with barriers designed to keep out dangerous pathogens. But protection comes at a cost: These barriers interfere with the immune system when faced with dire threats such glioblastoma, a deadly brain tumor for which there are few effective treatments.

Yale researchers have found a novel way to circumvent the brain's natural defenses when they're counterproductive by slipping immune system rescuers through the fortresses' drainage system, they report Jan. 15 in the journal Nature.

"People had thought there was very little the immune system could do to combat brain tumors," said senior corresponding author Akiko Iwasaki. "There has been no way for glioblastoma patients to benefit from immunotherapy."

Iwasaki is the Waldemar Von Zedtwitz Professor of Immunobiology and professor of molecular, cellular, and developmental biology and an investigator for the Howard Hughes Medical Institute.

While the brain itself has no direct way for disposing of cellular waste, tiny vessels lining the interior of the skull collect tissue waste and dispose of it through the body's lymphatic system, which filters toxins and waste from the body. It is this disposal system that researchers exploited in the new study.

These vessels form shortly after birth, spurred in part by the gene known as vascular endothelial growth factor C, or VEGF-C.

Yale's Jean-Leon Thomas, associate professor of neurology at Yale and senior co-corresponding author of the paper, wondered whether VEGF-C might increase immune response if lymphatic drainage was increased. And lead author Eric Song, a student working in Iwasaki's lab, wanted to see if VEGF-C could specifically be used to increase the immune system's surveillance of glioblastoma tumors. Together, the team investigated whether introducing VEGF-C through this drainage system would specifically target brain tumors.

The team introduced VEGF C into the cerebrospinal fluid of mice with glioblastoma and observed an increased level of T cell response to tumors in the brain. When combined with immune system checkpoint inhibitors commonly used in immunotherapy, the VEGF-C treatment significantly extended survival of the mice. In other words, the introduction of VEGF-C, in conjunction with cancer immunotherapy drugs, was apparently sufficient to target brain tumors.

"These results are remarkable," Iwasaki said. "We would like to bring this treatment to glioblastoma patients. The prognosis with current therapies of surgery and chemotherapy is still so bleak."

The study was primarily funded by the Howard Hughes Medical Institute and the National Institutes of Health.

Other Yale authors are Tianyang Mao, Huiping Dong, Ligia Simoes,Braga Boisserand, and Marcus Bosenberg. Salli Antila and Kari Alitalo of the University of Helsinki are also authors.

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Materials provided by Yale University. Original written by Bill Hathaway. Note: Content may be edited for style and length.

Scientists breach brain barriers to attack tumors

Illustration of human brain and tumor (stock image).

The brain is a sort of fortress, equipped with barriers designed to keep out dangerous pathogens. But protection comes at a cost: These barriers interfere with the immune system when faced with dire threats such glioblastoma, a deadly brain tumor for which there are few effective treatments.

Yale researchers have found a novel way to circumvent the brain's natural defenses when they're counterproductive by slipping immune system rescuers through the fortresses' drainage system, they report Jan. 15 in the journal Nature.

"People had thought there was very little the immune system could do to combat brain tumors," said senior corresponding author Akiko Iwasaki. "There has been no way for glioblastoma patients to benefit from immunotherapy."

Iwasaki is the Waldemar Von Zedtwitz Professor of Immunobiology and professor of molecular, cellular, and developmental biology and an investigator for the Howard Hughes Medical Institute.

While the brain itself has no direct way for disposing of cellular waste, tiny vessels lining the interior of the skull collect tissue waste and dispose of it through the body's lymphatic system, which filters toxins and waste from the body. It is this disposal system that researchers exploited in the new study.

These vessels form shortly after birth, spurred in part by the gene known as vascular endothelial growth factor C, or VEGF-C.

Yale's Jean-Leon Thomas, associate professor of neurology at Yale and senior co-corresponding author of the paper, wondered whether VEGF-C might increase immune response if lymphatic drainage was increased. And lead author Eric Song, a student working in Iwasaki's lab, wanted to see if VEGF-C could specifically be used to increase the immune system's surveillance of glioblastoma tumors. Together, the team investigated whether introducing VEGF-C through this drainage system would specifically target brain tumors.

The team introduced VEGF C into the cerebrospinal fluid of mice with glioblastoma and observed an increased level of T cell response to tumors in the brain. When combined with immune system checkpoint inhibitors commonly used in immunotherapy, the VEGF-C treatment significantly extended survival of the mice. In other words, the introduction of VEGF-C, in conjunction with cancer immunotherapy drugs, was apparently sufficient to target brain tumors.

"These results are remarkable," Iwasaki said. "We would like to bring this treatment to glioblastoma patients. The prognosis with current therapies of surgery and chemotherapy is still so bleak."

The study was primarily funded by the Howard Hughes Medical Institute and the National Institutes of Health.

Other Yale authors are Tianyang Mao, Huiping Dong, Ligia Simoes,Braga Boisserand, and Marcus Bosenberg. Salli Antila and Kari Alitalo of the University of Helsinki are also authors.

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Materials provided by Yale University. Original written by Bill Hathaway. Note: Content may be edited for style and length.

Scientists find oldest-known fossilized digestive tract -- 550 million years

A 550-million-year-old fossilized digestive tract found in the Nevada desert could be a key find in understanding the early history of animals on Earth.

Over a half-billion years ago, life on Earth was composed of simple ocean organisms unlike anything living in today's oceans. Then, beginning about 540 million years ago, animal structures changed dramatically.

During this time, ancestors of many animal groups we know today appeared, such as primitive crustaceans and worms, yet for years scientists did not know how these two seemingly unrelated communities of animals were connected, until now. An analysis of tubular fossils by scientists led by Jim Schiffbauer at the University of Missouri provides evidence of a 550 million-year-old digestive tract -- one of the oldest known examples of fossilized internal anatomical structures -- and reveals what scientists believe is a possible answer to the question of how these animals are connected.

The study was published in Nature Communications, a journal of Nature.

"Not only are these structures the oldest guts yet discovered, but they also help to resolve the long-debated evolutionary positioning of this important fossil group," said Schiffbauer, an associate professor of geological sciences in the MU College of Arts and Science and director of the X-ray Microanalysis Core facility. "These fossils fit within a very recognizable group of organisms -- the cloudinids -- that scientists use to identify the last 10 to 15 million years of the Ediacaran Period, or the period of time just before the Cambrian Explosion. We can now say that their anatomical structure appears much more worm-like than coral-like."

The Cambrian Explosion is widely considered by scientists to be the point in history of life on Earth when the ancestors of many animal groups we know today emerged.

In the study, the scientists used MU's X-ray Microanalysis Core facility to take a unique analytical approach for geological science -- micro-CT imaging -- that created a digital 3D image of the fossil. This technique allowed the scientists to view what was inside the fossil structure.

"With CT imaging, we can quickly assess key internal features and then analyze the entire fossil without potentially damaging it," said co-author Tara Selly, a research assistant professor in the Department of Geological Sciences and assistant director of the X-ray Microanalysis Core facility.

The study, "Discovery of bilaterian-type through-guts in cloudinomorphs from the terminal Ediacaran Period," was published in Nature Communications. Other authors include Sarah Jacquet from MU; Rachel Merz from Swarthmore College; Michael Strange from the University of Nevada, Las Vegas; Yaoping Cai from Northwest University in Xi'an, China; and Lyle Nelson and Emmy Smith from Johns Hopkins University.

Funding was provided by grants from the NSF Sedimentary Geology and Paleobiology Program (CAREER 1652351) and Instrumentation and Facilities Program (1636643). The content is solely the responsibility of the authors and does not necessarily represent the official views of the funding agencies.

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Materials provided by University of Missouri-Columbia. Note: Content may be edited for style and length.

Scientists discover key neural circuit regulating alcohol consumption

Scientists discover key neural circuit regulating alcohol consumption

Scientists have known that a region of the brain called the central nucleus of the amygdala (CeA) plays a role in behaviors related to alcohol use and consumption in general. It's been less known which precise populations of brain cells and their projections to other brain regions mediate these behaviors. Now, UNC School of Medicine scientists discovered that specific neurons in the CeA contribute to reward-like behaviors, alcohol consumption in particular.

Published in the Journal of Neuroscience, this research pinpoints a specific neural circuit that when altered caused animal models to drink less alcohol.

"The fact that these neurons promote reward-like behavior, that extremely low levels of alcohol consumption activate these cells, and that activation of these neurons drive alcohol drinking in animals without extensive prior drinking experience suggests that they may be important for early alcohol use and reward," said senior author Zoe McElligott, PhD, assistant professor of psychiatry and pharmacology. "It's our hope that by understanding the function of this circuit, we can better predict what happens in the brains of people who transition from casual alcohol use to subsequent abuse of alcohol, and the development of alcohol use disorders."

McElligott, who is also a member of the UNC Bowles Center for Alcohol Studies, set out to investigate if a population of neurons that express a specific neuropeptide (neurotensin or NTS) contributes to reward-like behaviors and alcohol drinking. She was especially interested in these neurons in the context of inexperienced alcohol use, such as when a person first begins to drink alcohol. Also, NTS neurons are a subpopulation of other neurons in this CeA brain region that have been implicated in anxiety and fear -- known as the somatostatin and corticotropin releasing factor neurons.

Using modern genetic and viral technologies in male mice, McElligott and colleagues found that selectively lesioning or ablating the NTS neurons in the CeA, while maintaining other types of CeA neurons, would cause the animals to drink less alcohol. This manipulation did not alter anxiety-like behavior. It also did not affect the consumption of other palatable liquids such as sucrose, saccharin, and bitter quinine solutions.

"We found that these NTS neurons in the CeA send a strong projection to the hindbrain, where they inhibit the parabrachial nucleus, near the brainstem," McElligott said.

Using optogenetics -- a technique where light activates these neurons -- the researchers stimulated the terminal projections of the CeA-NTS neurons in the parabrachial and found that this stimulation inhibited the neurons in the parabrachial. When the scientists stimulated this projection with a laser in one half of the animal's box, animals would spend more time where the stimulation would occur.

Animals also learned to perform a task to get the laser stimulation to turn on, and they would do this repeatedly, suggesting that they found this stimulation to be rewarding.

"Furthermore, when we stimulated this projection, animals would drink more alcohol as compared to when they had an opportunity to drink alcohol without laser stimulation," McElligott said. "In contrast to our study where we ablated the NTS neurons, laser stimulation of this parabrachial pathway also caused the animals to consume caloric and non-caloric sweetened beverages. When the animals were presented with regular food and a sweet food, however, laser stimulation did not enhance the consumption regardless of the mouse's hunger state. This suggests that different circuits may regulate the consumption of rewarding fluids and solids."

McElligott and her graduate student María Luisa Torruella Suarez, the first author of this study, hope to explore how alcohol experience may change these neurons over time.

"Would these cells respond differently after animals have been drinking high quantities of alcohol over time?" McElligott said. "We also want to discover which populations of neurons in the parabrachial are receiving inputs from these neurons. Fully understanding this circuit could be the key to developing therapeutics to help people with alcohol use disorders."

The National Institutes of Health, The North Carolina Translational Clinical Science (NC TraCS) Institute, the Alcohol Beverage Medical Research Foundation, and The UNC Bowles Center for Alcohol Studies funded this research.

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Materials provided by University of North Carolina Health Care. Note: Content may be edited for style and length.

Scientists discover key neural circuit regulating alcohol consumption

Scientists discover key neural circuit regulating alcohol consumption

Scientists have known that a region of the brain called the central nucleus of the amygdala (CeA) plays a role in behaviors related to alcohol use and consumption in general. It's been less known which precise populations of brain cells and their projections to other brain regions mediate these behaviors. Now, UNC School of Medicine scientists discovered that specific neurons in the CeA contribute to reward-like behaviors, alcohol consumption in particular.

Published in the Journal of Neuroscience, this research pinpoints a specific neural circuit that when altered caused animal models to drink less alcohol.

"The fact that these neurons promote reward-like behavior, that extremely low levels of alcohol consumption activate these cells, and that activation of these neurons drive alcohol drinking in animals without extensive prior drinking experience suggests that they may be important for early alcohol use and reward," said senior author Zoe McElligott, PhD, assistant professor of psychiatry and pharmacology. "It's our hope that by understanding the function of this circuit, we can better predict what happens in the brains of people who transition from casual alcohol use to subsequent abuse of alcohol, and the development of alcohol use disorders."

McElligott, who is also a member of the UNC Bowles Center for Alcohol Studies, set out to investigate if a population of neurons that express a specific neuropeptide (neurotensin or NTS) contributes to reward-like behaviors and alcohol drinking. She was especially interested in these neurons in the context of inexperienced alcohol use, such as when a person first begins to drink alcohol. Also, NTS neurons are a subpopulation of other neurons in this CeA brain region that have been implicated in anxiety and fear -- known as the somatostatin and corticotropin releasing factor neurons.

Using modern genetic and viral technologies in male mice, McElligott and colleagues found that selectively lesioning or ablating the NTS neurons in the CeA, while maintaining other types of CeA neurons, would cause the animals to drink less alcohol. This manipulation did not alter anxiety-like behavior. It also did not affect the consumption of other palatable liquids such as sucrose, saccharin, and bitter quinine solutions.

"We found that these NTS neurons in the CeA send a strong projection to the hindbrain, where they inhibit the parabrachial nucleus, near the brainstem," McElligott said.

Using optogenetics -- a technique where light activates these neurons -- the researchers stimulated the terminal projections of the CeA-NTS neurons in the parabrachial and found that this stimulation inhibited the neurons in the parabrachial. When the scientists stimulated this projection with a laser in one half of the animal's box, animals would spend more time where the stimulation would occur.

Animals also learned to perform a task to get the laser stimulation to turn on, and they would do this repeatedly, suggesting that they found this stimulation to be rewarding.

"Furthermore, when we stimulated this projection, animals would drink more alcohol as compared to when they had an opportunity to drink alcohol without laser stimulation," McElligott said. "In contrast to our study where we ablated the NTS neurons, laser stimulation of this parabrachial pathway also caused the animals to consume caloric and non-caloric sweetened beverages. When the animals were presented with regular food and a sweet food, however, laser stimulation did not enhance the consumption regardless of the mouse's hunger state. This suggests that different circuits may regulate the consumption of rewarding fluids and solids."

McElligott and her graduate student María Luisa Torruella Suarez, the first author of this study, hope to explore how alcohol experience may change these neurons over time.

"Would these cells respond differently after animals have been drinking high quantities of alcohol over time?" McElligott said. "We also want to discover which populations of neurons in the parabrachial are receiving inputs from these neurons. Fully understanding this circuit could be the key to developing therapeutics to help people with alcohol use disorders."

The National Institutes of Health, The North Carolina Translational Clinical Science (NC TraCS) Institute, the Alcohol Beverage Medical Research Foundation, and The UNC Bowles Center for Alcohol Studies funded this research.

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Story Source:

Materials provided by University of North Carolina Health Care. Note: Content may be edited for style and length.

Scientists discover key neural circuit regulating alcohol consumption

Scientists discover key neural circuit regulating alcohol consumption

Scientists have known that a region of the brain called the central nucleus of the amygdala (CeA) plays a role in behaviors related to alcohol use and consumption in general. It's been less known which precise populations of brain cells and their projections to other brain regions mediate these behaviors. Now, UNC School of Medicine scientists discovered that specific neurons in the CeA contribute to reward-like behaviors, alcohol consumption in particular.

Published in the Journal of Neuroscience, this research pinpoints a specific neural circuit that when altered caused animal models to drink less alcohol.

"The fact that these neurons promote reward-like behavior, that extremely low levels of alcohol consumption activate these cells, and that activation of these neurons drive alcohol drinking in animals without extensive prior drinking experience suggests that they may be important for early alcohol use and reward," said senior author Zoe McElligott, PhD, assistant professor of psychiatry and pharmacology. "It's our hope that by understanding the function of this circuit, we can better predict what happens in the brains of people who transition from casual alcohol use to subsequent abuse of alcohol, and the development of alcohol use disorders."

McElligott, who is also a member of the UNC Bowles Center for Alcohol Studies, set out to investigate if a population of neurons that express a specific neuropeptide (neurotensin or NTS) contributes to reward-like behaviors and alcohol drinking. She was especially interested in these neurons in the context of inexperienced alcohol use, such as when a person first begins to drink alcohol. Also, NTS neurons are a subpopulation of other neurons in this CeA brain region that have been implicated in anxiety and fear -- known as the somatostatin and corticotropin releasing factor neurons.

Using modern genetic and viral technologies in male mice, McElligott and colleagues found that selectively lesioning or ablating the NTS neurons in the CeA, while maintaining other types of CeA neurons, would cause the animals to drink less alcohol. This manipulation did not alter anxiety-like behavior. It also did not affect the consumption of other palatable liquids such as sucrose, saccharin, and bitter quinine solutions.

"We found that these NTS neurons in the CeA send a strong projection to the hindbrain, where they inhibit the parabrachial nucleus, near the brainstem," McElligott said.

Using optogenetics -- a technique where light activates these neurons -- the researchers stimulated the terminal projections of the CeA-NTS neurons in the parabrachial and found that this stimulation inhibited the neurons in the parabrachial. When the scientists stimulated this projection with a laser in one half of the animal's box, animals would spend more time where the stimulation would occur.

Animals also learned to perform a task to get the laser stimulation to turn on, and they would do this repeatedly, suggesting that they found this stimulation to be rewarding.

"Furthermore, when we stimulated this projection, animals would drink more alcohol as compared to when they had an opportunity to drink alcohol without laser stimulation," McElligott said. "In contrast to our study where we ablated the NTS neurons, laser stimulation of this parabrachial pathway also caused the animals to consume caloric and non-caloric sweetened beverages. When the animals were presented with regular food and a sweet food, however, laser stimulation did not enhance the consumption regardless of the mouse's hunger state. This suggests that different circuits may regulate the consumption of rewarding fluids and solids."

McElligott and her graduate student María Luisa Torruella Suarez, the first author of this study, hope to explore how alcohol experience may change these neurons over time.

"Would these cells respond differently after animals have been drinking high quantities of alcohol over time?" McElligott said. "We also want to discover which populations of neurons in the parabrachial are receiving inputs from these neurons. Fully understanding this circuit could be the key to developing therapeutics to help people with alcohol use disorders."

The National Institutes of Health, The North Carolina Translational Clinical Science (NC TraCS) Institute, the Alcohol Beverage Medical Research Foundation, and The UNC Bowles Center for Alcohol Studies funded this research.

---

Story Source:

Materials provided by University of North Carolina Health Care. Note: Content may be edited for style and length.

Scientists discover key neural circuit regulating alcohol consumption

Scientists have known that a region of the brain called the central nucleus of the amygdala (CeA) plays a role in behaviors related to alcohol use and consumption in general. It's been less known which precise populations of brain cells and their projections to other brain regions mediate these behaviors. Now, UNC School of Medicine scientists discovered that specific neurons in the CeA contribute to reward-like behaviors, alcohol consumption in particular.

Published in the Journal of Neuroscience, this research pinpoints a specific neural circuit that when altered caused animal models to drink less alcohol.

"The fact that these neurons promote reward-like behavior, that extremely low levels of alcohol consumption activate these cells, and that activation of these neurons drive alcohol drinking in animals without extensive prior drinking experience suggests that they may be important for early alcohol use and reward," said senior author Zoe McElligott, PhD, assistant professor of psychiatry and pharmacology. "It's our hope that by understanding the function of this circuit, we can better predict what happens in the brains of people who transition from casual alcohol use to subsequent abuse of alcohol, and the development of alcohol use disorders."

McElligott, who is also a member of the UNC Bowles Center for Alcohol Studies, set out to investigate if a population of neurons that express a specific neuropeptide (neurotensin or NTS) contributes to reward-like behaviors and alcohol drinking. She was especially interested in these neurons in the context of inexperienced alcohol use, such as when a person first begins to drink alcohol. Also, NTS neurons are a subpopulation of other neurons in this CeA brain region that have been implicated in anxiety and fear -- known as the somatostatin and corticotropin releasing factor neurons.

Using modern genetic and viral technologies in male mice, McElligott and colleagues found that selectively lesioning or ablating the NTS neurons in the CeA, while maintaining other types of CeA neurons, would cause the animals to drink less alcohol. This manipulation did not alter anxiety-like behavior. It also did not affect the consumption of other palatable liquids such as sucrose, saccharin, and bitter quinine solutions.

"We found that these NTS neurons in the CeA send a strong projection to the hindbrain, where they inhibit the parabrachial nucleus, near the brainstem," McElligott said.

Using optogenetics -- a technique where light activates these neurons -- the researchers stimulated the terminal projections of the CeA-NTS neurons in the parabrachial and found that this stimulation inhibited the neurons in the parabrachial. When the scientists stimulated this projection with a laser in one half of the animal's box, animals would spend more time where the stimulation would occur.

Animals also learned to perform a task to get the laser stimulation to turn on, and they would do this repeatedly, suggesting that they found this stimulation to be rewarding.

"Furthermore, when we stimulated this projection, animals would drink more alcohol as compared to when they had an opportunity to drink alcohol without laser stimulation," McElligott said. "In contrast to our study where we ablated the NTS neurons, laser stimulation of this parabrachial pathway also caused the animals to consume caloric and non-caloric sweetened beverages. When the animals were presented with regular food and a sweet food, however, laser stimulation did not enhance the consumption regardless of the mouse's hunger state. This suggests that different circuits may regulate the consumption of rewarding fluids and solids."

McElligott and her graduate student María Luisa Torruella Suarez, the first author of this study, hope to explore how alcohol experience may change these neurons over time.

"Would these cells respond differently after animals have been drinking high quantities of alcohol over time?" McElligott said. "We also want to discover which populations of neurons in the parabrachial are receiving inputs from these neurons. Fully understanding this circuit could be the key to developing therapeutics to help people with alcohol use disorders."

The National Institutes of Health, The North Carolina Translational Clinical Science (NC TraCS) Institute, the Alcohol Beverage Medical Research Foundation, and The UNC Bowles Center for Alcohol Studies funded this research.

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Scientists inch closer than ever to signal from cosmic dawn

Scientists inch closer than ever to signal from cosmic dawn

Around 12 billion years ago, the universe emerged from a great cosmic dark age as the first stars and galaxies lit up. With a new analysis of data collected by the Murchison Widefield Array (MWA) radio telescope, scientists are now closer than ever to detecting the ultra-faint signature of this turning point in cosmic history.

In a paper on the preprint site ArXiv and soon to be published in the Astrophysical Journal, researchers present the first analysis of data from a new configuration of the MWA designed specifically to look for the signal of neutral hydrogen, the gas that dominated the universe during the cosmic dark age. The analysis sets a new limit -- the lowest limit yet -- for the strength of the neutral hydrogen signal.

"We can say with confidence that if the neutral hydrogen signal was any stronger than the limit we set in the paper, then the telescope would have detected it," said Jonathan Pober, an assistant professor of physics at Brown University and corresponding author on the new paper. "These findings can help us to further constrain the timing of when the cosmic dark ages ended and the first stars emerged."

The research was led by Wenyang Li, who performed the work as a Ph.D. student at Brown. Li and Pober collaborated with an international group of researchers working with the MWA.

Despite its importance in cosmic history, little is known about the period when the first stars formed, which is known as the Epoch of Reionization (EoR). The first atoms that formed after the Big Bang were positively charged hydrogen ions -- atoms whose electrons were stripped away by the energy of the infant universe. As the universe cooled and expanded, hydrogen atoms reunited with their electrons to form neutral hydrogen. And that's just about all there was in the universe until about 12 billion years ago, when atoms started clumping together to form stars and galaxies. Light from those objects re-ionized the neutral hydrogen, causing it to largely disappear from interstellar space.

The goal of projects like the one happening at MWA is to locate the signal of neutral hydrogen from the dark ages and measure how it changed as the EoR unfolded. Doing so could reveal new and critical information about the first stars -- the building blocks of the universe we see today. But catching any glimpse of that 12-billion-year-old signal is a difficult task that requires instruments with exquisite sensitivity.

When it began operating in 2013, the MWA was an array of 2,048 radio antennas arranged across the remote countryside of Western Australia. The antennas are bundled together into 128 "tiles," whose signals are combined by a supercomputer called the Correlator. In 2016, the number of tiles was doubled to 256, and their configuration across the landscape was altered to improve their sensitivity to the neutral hydrogen signal. This new paper is the first analysis of data from the expanded array.

Neutral hydrogen emits radiation at a wavelength of 21 centimeters. As the universe has expanded over the past 12 billion years, the signal from the EoR is now stretched to about 2 meters, and that's what MWA astronomers are looking for. The problem is there are myriad other sources that emit at the same wavelength -- human-made sources like digital television as well as natural sources from within the Milky Way and from millions of other galaxies.

"All of these other sources are many orders of magnitude stronger than the signal we're trying to detect," Pober said. "Even an FM radio signal that's reflected off an airplane that happens to be passing above the telescope is enough to contaminate the data."

To home in on the signal, the researchers use a myriad of processing techniques to weed out those contaminants. At the same time, they account for the unique frequency responses of the telescope itself.

"If we look at different radio frequencies or wavelengths, the telescope behaves a little differently," Pober said. "Correcting for the telescope response is absolutely critical for then doing the separation of astrophysical contaminants and the signal of interest."

Those data analysis techniques combined with the expanded capacity of the telescope itself resulted in a new upper bound of the EoR signal strength. It's the second consecutive best-limit-to-date analysis to be released by MWA and raises hope that the experiment will one day detect the elusive EoR signal.

"This analysis demonstrates that the phase two upgrade had a lot of its desired effects and that the new analysis techniques will improve future analyses," Pober said. "The fact that MWA has now published back-to-back the two best limits on the signal gives momentum to the idea that this experiment and its approach has a lot of promise."

The research was supported in part by the U.S. National Science Foundation (grant #1613040). The MWA receives support from the Australian government and acknowledges Wajarri Yamatji people as the traditional owners of the observatory site.

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With Mars methane mystery unsolved, Curiosity serves scientists a new one: Oxygen

Curiosity serves scientists a new one: Oxygen

For the first time in the history of space exploration, scientists have measured the seasonal changes in the gases that fill the air directly above the surface of Gale Crater on Mars. As a result, they noticed something baffling: oxygen, the gas many Earth creatures use to breathe, behaves in a way that so far scientists cannot explain through any known chemical processes.

Over the course of three Mars years (or nearly six Earth years) an instrument in the Sample Analysis at Mars (SAM) portable chemistry lab inside the belly of NASA's Curiosity rover inhaled the air of Gale Crater and analyzed its composition. The results SAM spit out confirmed the makeup of the Martian atmosphere at the surface: 95% by volume of carbon dioxide (CO2), 2.6% molecular nitrogen (N2), 1.9% argon (Ar), 0.16% molecular oxygen (O2), and 0.06% carbon monoxide (CO). They also revealed how the molecules in the Martian air mix and circulate with the changes in air pressure throughout the year. These changes are caused when CO2 gas freezes over the poles in the winter, thereby lowering the air pressure across the planet following redistribution of air to maintain pressure equilibrium. When CO2 evaporates in the spring and summer and mixes across Mars, it raises the air pressure.

Within this environment, scientists found that nitrogen and argon follow a predictable seasonal pattern, waxing and waning in concentration in Gale Crater throughout the year relative to how much CO2 is in the air. They expected oxygen to do the same. But it didn't. Instead, the amount of the gas in the air rose throughout spring and summer by as much as 30%, and then dropped back to levels predicted by known chemistry in fall. This pattern repeated each spring, though the amount of oxygen added to the atmosphere varied, implying that something was producing it and then taking it away.

"The first time we saw that, it was just mind boggling," said Sushil Atreya, professor of climate and space sciences at the University of Michigan in Ann Arbor. Atreya is a co-author of a paper on this topic published on November 12 in the Journal of Geophysical Research: Planets.

As soon as scientists discovered the oxygen enigma, Mars experts set to work trying to explain it. They first double- and triple-checked the accuracy of the SAM instrument they used to measure the gases: the Quadrupole Mass Spectrometer. The instrument was fine. They considered the possibility that CO2 or water (H2O) molecules could have released oxygen when they broke apart in the atmosphere, leading to the short-lived rise. But it would take five times more water above Mars to produce the extra oxygen, and CO2 breaks up too slowly to generate it over such a short time. What about the oxygen decrease? Could solar radiation have broken up oxygen molecules into two atoms that blew away into space? No, scientists concluded, since it would take at least 10 years for the oxygen to disappear through this process.

"We're struggling to explain this," said Melissa Trainer, a planetary scientist at NASA's Goddard Space Flight Center in Greenbelt, Maryland who led this research. "The fact that the oxygen behavior isn't perfectly repeatable every season makes us think that it's not an issue that has to do with atmospheric dynamics. It has to be some chemical source and sink that we can't yet account for."

To scientists who study Mars, the oxygen story is curiously similar to that of methane. Methane is constantly in the air inside Gale Crater in such small quantities (0.00000004% on average) that it's barely discernable even by the most sensitive instruments on Mars. Still, it's been measured by SAM's Tunable Laser Spectrometer. The instrument revealed that while methane rises and falls seasonally, it increases in abundance by about 60% in summer months for inexplicable reasons. (In fact, methane also spikes randomly and dramatically. Scientists are trying to figure out why.)

With the new oxygen findings in hand, Trainer's team is wondering if chemistry similar to what's driving methane's natural seasonal variations may also drive oxygen's. At least occasionally, the two gases appear to fluctuate in tandem.

"We're beginning to see this tantalizing correlation between methane and oxygen for a good part of the Mars year," Atreya said. "I think there's something to it. I just don't have the answers yet. Nobody does."

Oxygen and methane can be produced both biologically (from microbes, for instance) and abiotically (from chemistry related to water and rocks). Scientists are considering all options, although they don't have any convincing evidence of biological activity on Mars. Curiosity doesn't have instruments that can definitively say whether the source of the methane or oxygen on Mars is biological or geological. Scientists expect that non-biological explanations are more likely and are working diligently to fully understand them.

Trainer's team considered Martian soil as a source of the extra springtime oxygen. After all, it's known to be rich in the element, in the form of compounds such as hydrogen peroxide and perchlorates. One experiment on the Viking landers showed decades ago that heat and humidity could release oxygen from Martian soil. But that experiment took place in conditions quite different from the Martian spring environment, and it doesn't explain the oxygen drop, among other problems. Other possible explanations also don't quite add up for now. For example, high-energy radiation of the soil could produce extra O2 in the air, but it would take a million years to accumulate enough oxygen in the soil to account for the boost measured in only one spring, the researchers report in their paper.

"We have not been able to come up with one process yet that produces the amount of oxygen we need, but we think it has to be something in the surface soil that changes seasonally because there aren't enough available oxygen atoms in the atmosphere to create the behavior we see," said Timothy McConnochie, assistant research scientist at the University of Maryland in College Park and another co-author of the paper.

The only previous spacecraft with instruments capable of measuring the composition of the Martian air near the ground were NASA's twin Viking landers, which arrived on the planet in 1976. The Viking experiments covered only a few Martian days, though, so they couldn't reveal seasonal patterns of the different gases. The new SAM measurements are the first to do so. The SAM team will continue to measure atmospheric gases so scientists can gather more detailed data throughout each season. In the meantime, Trainer and her team hope that other Mars experts will work to solve the oxygen mystery.

"This is the first time where we're seeing this interesting behavior over multiple years. We don't totally understand it," Trainer said. "For me, this is an open call to all the smart people out there who are interested in this: See what you can come up with."

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