News

M. Kerry O'Banion, M.D., Ph.D. has been awarded $1.8 million from NASA to explore the effect space travel has on the immune system and bone marrow, and how that impacts brain function.

The grant is one of 21 research proposals recently awarded by NASA to help answer questions about astronaut health and performance during future long-duration missions, including crewed missions to the Moon and Mars.

Using simulated space radiation produced by particle accelerators at the NASA Space Radiation Laboratory at Brookhaven National Laboratory on Long Island, O'Banion and his team will examine tissue and cellular changes in genes, blood flow, and immune cell function in mice. Behavioral tests and computer-assisted imaging will also be used to quantify damage and inflammation in the brain.

O'Banion -- Professor of Neuroscience and Neurology in the Del Monte Institute for Neuroscience -- and colleagues previously worked with NASA on a study that showed exposure to a particular form of space radiation called high-mass, high-charged particles caused biological and cognitive changes in mice suggesting an accelerated risk for the development of Alzheimer's disease.

This time around, O'Banion will be working with Laura Calvi, M.D., an endocrinologist and co-director of the UR Multidisciplinary Neuroendocrinology Clinic. Her preliminary data found space radiation changes in bone marrow suggestive of a skewed phenotype, in which white blood cells are changed into a more inflammatory phenotype. Similar changes are found with aging. "This helps to bind a common hypothesis about dysfunction and degeneration in multiple systems, with the bone marrow communicating to the brain through the vasculature," O'Banion said.

Researchers at the University of Rochester Medical Center (URMC) and Duke University Medical Center will collaborate on a study that investigates why some older patients, who become severely ill from COVID-19, develop delirium that can lead to brain damage and a dementia diagnosis.

Nearly 30-percent of patients hospitalized with COVID-19 develop delirium -- a state of confusion and impaired awareness. For severely ill patients the likelihood of delirium is closer to 70-percent. "The initial delirium, and then the cognitive, behavioral, and emotional problems -- commonly known as dysexecutive syndrome -- were arguably the most notable things in older people that had managed to survive COVID-19," said Harris Gelbard, M.D., Ph.D. Professor and Director, Center for Neurotherapeutics Discovery, who is also the principal investigator at URMC on this study which is being funded by the National Institute of Aging. "Nobody knows whether that's permanent or not because of the advanced age of the people this is impacting."

Using a model for inhaled lipopolysaccharide-based acute lung injury in mice to mimic what happens in the lungs of a severally ill COVID-19 patient, Gelbard and his colleague Niccolo Terrando, Ph.D. at Duke University Medical Center will look for specific events in the neurovascular unit —brain endothelial cells and their blood-brain barrier (BBB) forming tight junctions that support the central nervous system -- that can be traced back to cognitive impairment. Part of the hypothesis Gelbard is investigating is that scarring in the lung may cause platelets and inflammatory white cells to migrate to blood vessels in the central nervous system with the white cells traversing the BBB to cause neurologic disease. "The goal is to establish what the prerequisites are for lung injury that will lead to brain injury. And at that point, then we can start asking more complicated questions."

The researchers will also investigate how the body responds to URMC-099, an anti-inflammatory and neuroprotective agent developed by Gelbard, to prevent these sequelae. The use of behavior analysis at Duke and in vivo brain imaging at URMC will determine delirium-like changes in the mice.

Gelbard and Terrando are confident that this study will lead to a larger and longer study of the impact COVID-19 has on the brain of an older population. "If you could do something to prevent that in the first place, chances are you are going to do better, down the road."

We would like to congratulate Mark Stoessel from the Majewska Lab for being awarded an F31 grant for "Dynamics and function of cerebellar microglia". The grant runs from September 2020 - September 2023.

We also congratulate Dennisha King, Tori Popov, Mark DuHain, and MaKenna Cealie for their appointments to the new T32 grant.

Congratulations all. Well done.

Let's all send congratulations to our graduate students and faculty for once again being recognized at Convocation.

Graduate Alumni Fellowship Award - Paige Nicklas

Irving L. Spar Fellowship Award - Maleelo Shamambo

J. Newell Stannard Scholarship Award - Michael Giannetto

Merritt and Marjorie Cleveland Fellowship - Victoria Popov

Outstanding Graduate Program Director - Anna Majewska, Ph.D.

Outstanding Graduate Course Director - Robert Stanley Freeman, Ph.D.

Wake up microglia! How brain state regulates immune cells

Microglia, the immune cells of the brain, helps the brain modify its circuits in response to new experiences. In a recent study, we found that microglia helping to rewire the brain may be dependent on whether the organism is awake or asleep.

Historically, neuroscience focused on neurons, the functional cellular units of communication in the brain. However, exciting recent advances in microscopy have revealed the importance of many other cell types in essential brain functions. Amongst these supporting players in the brain are microglia, the immune cells of the brain.

Major NIH award to study how the brain infers structure from sensory signals may have applications for disorders like schizophrenia and offer insights for artificial intelligence

Imagine you're sitting on a train. You look out the window and see another train on an adjacent track that appears to be moving. But, has your train stopped while the other train is moving, or are you moving while the other train is stopped?

The same sensory experience—viewing a train—can yield two very different perceptions, leading you to feel either a sensation of yourself in motion or a sensation of being stationary while an object moves around you.

Human brains are constantly faced with such ambiguous sensory inputs. In order to resolve the ambiguity and correctly perceive the world, our brains employ a process known as causal inference.

Causal inference is a key to learning, reasoning, and decision making, but researchers currently know little about the neurons involved in the process.

In order to bridge the gap, a team of researchers at the University of Rochester, including Greg DeAngelis, the George Eastman Professor of Brain and Cognitive Sciences, and Ralf Haefner, an assistant professor of brain and cognitive sciences, received a $12.2 million grant award from the National Institutes of Health for a project to better understand how the brain uses causal inference to distinguish self-motion from object motion.

The five-year award is part of the NIH's Brain Research through Advancing Innovative Neurotechnologies (BRAIN) initiative. The insights generated by the award, which also involves researchers at New York University, Harvard Medical School, Rice University, and the University of Washington, may have important applications in developing treatments and therapies for neural disorders such as autism and schizophrenia, as well as inspire advances in artificial intelligence.

"This NIH BRAIN Initiative Award is the biggest research award in the history of the Department Brain and Cognitive Sciences," says Duje Tadin, professor and chair of the department at Rochester. "It aims to solve the key question of how our brains interpret the information collected by our senses. This research builds on a longstanding strength of BCS of using computational methods to understand both behavior and underlying neural mechanisms."

Unraveling a complicated circuit of neurons

Causal inference involves a complicated circuit of neurons and other sensory mechanisms that are not widely understood, DeAngelis says, because "sensory perception works so well most of the time, so we take for granted how difficult of a computational problem it is."

In actuality, sensory signals are noisy and incomplete. Additionally, there are many possible events that could happen in the world that would produce similar patterns of sensory input.

Consider a spot of light that moves across the retina of the eye. The same visual input could be the result of a variety of situations: it could be caused by an object that moves in the world while the viewer remains stationary, such as a person standing still at a window and observing a moving ambulance with a flashing light; it could be caused by a moving observer viewing a stationary object, such as a runner noticing a lamppost from a distance; or it could be caused by many different combinations of object motion, self-motion, and depth.

The brain has a difficult problem to solve: it must infer what most likely caused the specific pattern of sensory signals that it received. It can then draw conclusions about the situation and plan appropriate actions in response.

Using data science, lab experiments, computer models, and cognitive theory, DeAngelis, Haefner, and their colleagues will pinpoint single neurons and groups of neurons that are involved in the process. Their goal is to identify how the brain generates a consistent view of reality through interactions between the parts of the brain that process sensory stimuli and the parts of the brain that make decisions and plan actions.

Developing therapies and artificial intelligence

Recognizing how the brain uses causal inference to separate self-motion from object motion may help in designing artificial intelligence and autopilot devices.

"Understanding how the brain infers self-motion and object motion might provide inspiration for improving existing algorithms for autopilot devices on planes and self-driving cars," Haefner says.

For example, a plane's circuitry must take into account the plane's self-motion in the air while also avoiding other moving planes appearing around it.

The research may additionally have important applications in developing treatments and therapies for neural disorders such as autism and schizophrenia, conditions in which casual inference is thought to be impaired.

"While the project is basic science focused on understanding the fundamental mechanisms of causal inference, this knowledge should eventually be applicable to the treatment of these disorders," DeAngelis says.

New research details how the complex set of molecular and fluid dynamics that comprise the glymphatic system -- the brain's unique process of waste removal -- are synchronized with the master internal clock that regulates the sleep-wake cycle. These findings suggest that people who rely on sleeping during daytime hours are at greater risk for developing neurological disorders.

"These findings show that glymphatic system function is not solely based on sleep or wakefulness, but by the daily rhythms dictated by our biological clock," said neuroscientist Maiken Nedergaard, M.D., D.M.Sc., co-director of the Center for Translational Neuromedicine at the University of Rochester Medical Center (URMC) and senior author of the study, which appears in the journal Nature Communications.

The findings add to a growing understanding of the operation and function of glymphatic system, the brain's self-contained waste removal process which was first discovered in 2012 by researchers in the Nedergaard's lab. The system consists of a network of plumbing that follows the path of blood vessels and pumps cerebrospinal fluid (CSF) through brain tissue, washing away waste. Research a few years later showed that the glymphatic system primarily functions while we sleep.

Since those initial discoveries, Nedergaard's lab and others have shown the role that blood pressure, heart rate, circadian timing, and depth of sleep play in the glymphatic system's function and the chemical signaling that occurs in the brain to turn the system on and off. They have also shown how disrupted sleep or trauma can cause the system to break down and allow toxic proteins to accumulate in the brain, potentially giving rise to a number of neurodegenerative diseases, such as Alzheimer's.

Vision scientist David Williams is third consecutive recipient with Rochester ties.

For the third consecutive year, a member of the Rochester community has been recognized by the Association of University Professors of Ophthalmology (AUPO) for outstanding vision research.

David Williams, the William G. Allyn Professor of Medical Optics, has been selected by the association as the 2021 recipient of the RPB David F. Weeks Award for Outstanding Vision Research. The award annually recognizes and celebrates an outstanding ophthalmic vision scientist whose research has made meaningful contributions to the understanding or treatment of potentially blinding eye diseases.

The previous two recipients of the award were:

2020: Christine Curcio '81 (PhD), who is now the White-McKee Endowed Professor in Ophthalmology at the University of Alabama and director of the Age-Related Macular Degeneration Histopathology Lab.

2019: Jayakrishna Ambati '98M (Res), who is now a professor of ophthalmology at the University of Virginia.

Williams, who holds joint appointments in optics, brain and cognitive sciences, ophthalmology, and biomedical engineering, is widely regarded as one of the world's leading experts on human vision. As a pioneer in using new technologies that improve the eyesight of people around the world, he and his research team demonstrated the first adaptive optics system for the eye, making it possible to image individual retinal cells. The techniques developed by Williams and his group have also improved vision in patients with contact lenses, intraocular lenses, and laser refractive surgery. For example, the methods Williams's group developed are used in many of the Lasik procedures conducted worldwide today.

Williams additionally serves as director of the Center for Visual Science, a research program consisting of more than 37 faculty members from seven different departments dedicated to understanding how humans see, as well as the disorders that compromise sight.

Williams joined the Rochester faculty in 1981, and served as dean for research in Arts, Sciences & Engineering from 2011 to 2019. He is a fellow of the Association for Research in Vision and Ophthalmology, the Optical Society of America, and the American Association for the Advancement of Science. In 2017, he was named a member of the National Academy of Sciences.

The Weeks Award is scheduled to be presented to Williams at the AUPO Annual Meeting in February 2021.

A new study, from the journal Current Biology, spotlights research from Biomedical Genetics Professor Douglas Portman, Ph.D. Titled Dynamic, Non-binary Specification of Sexual State in the C. elegans Nervous System, this research "identifies a genetic switch in brain cells that can toggle between sex-specific states when necessary, findings that question the idea of sex as a fixed property". Further information can be found on the URMC's Del Monte Institute's webpage: NeURoscience.

Visit the NeURscience Blog where Neuroscience Graduate Program students are interviewed on their perspective of the future of Neuroscience.

The University of Rochester has been designated an Intellectual and Developmental Disabilities Research Center (IDDRC) by the National Institute of Child Health and Human Development (NICHD). The award recognizes the Medical Center's national leadership in research for conditions such Autism, Batten disease, and Rett syndrome, will translate scientific insights into new ways to diagnose and treat these conditions, and provide patients and families access to cutting edge care.

The IDDRC at the University of Rochester will be led by John Foxe, Ph.D., director of the Del Monte Institute for Neuroscience, and Jonathan Mink, M.D., Ph.D., chief of Child Neurology at Golisano Children's Hospital. The designation is accompanied with more than $6 million in funding from NICHD.

New Rochester research indicates some neurons may be more adept than previously thought in helping you perceive the motion of objects while you move through the world.

The findings may have implications for developing future prosthetics and for understanding some brain disorders.

Our brains use various reference frames—also known as coordinate systems—to represent the motion of objects in a scene.

Some coordinate systems are more useful than others for representing information. To represent a location on Earth, for example, we might use an Earth-centered coordinate system such as latitude and longitude. In such an Earth-centered coordinate system, a location—such as your home—is constant over time. But you could also represent where you live as a location relative to the sun using a sun-centered coordinate system. Such a system would clearly not be useful for people trying to find where you live, as your address in sun-centered coordinates would change continuously as the Earth rotates relative to the sun.

The human brain faces this same problem of representing information with appropriate coordinate systems and transferring between coordinate systems to guide your actions. This is partly because sensory information is encoded in different reference frames: visual information is initially encoded relative to the eye with eye-centered coordinates, auditory information is initially encoded relative to the head with head-centered coordinates, and so on. An interesting set of computations must occur in the brain in order for these sensory signals to be combined to allow a person to perceive an entire scene.

But how do neurons represent objects in different reference frames while you move through an environment?

In a paper published in the journal Nature Neuroscience, researchers from the University of Rochester, including Greg DeAngelis, a professor of brain and cognitive sciences, examined how neurons in the brain represent the motion of an object while the observer is also moving.

Specifically, the researchers studied how observers judge an object's motion relative to the observer's head or relative to the world.

Their findings—that neurons in a specific brain region are more flexible in switching between reference frames—offer important information about the inner workings of the brain and could potentially be used in neural prosthetics and therapies to treat brain disorders.

Are neurons fixed or flexible?

Imagine you're playing soccer. If you're running and want to head the ball, you would need to compute the trajectory of the ball's motion relative to your head so you can make contact between your head and the ball. A head-centered coordinate system would therefore be useful. Alternatively, if you are running and watching your teammate kick the ball toward the goal, you would need to compute the trajectory of the ball relative to the goal to determine whether or not your teammate scored. This would require a world-centered coordinate system since the goal is fixed relative to the world.

"Depending on the task being performed, the brain needs to represent object motion in different coordinate systems to be successful," DeAngelis says. "The big question is: how does the brain do this?"

The researchers wanted to determine if the brain has to switch between different neurons that each have a different fixed reference frame—for example, switching between head-centered neurons and world-centered neurons—or if the neurons are flexible and update their reference frames according to the instantaneous demands of the task of representing object motion.

The researchers trained subjects to judge object motion in either head-centered or world-centered coordinates and to switch between them from trial to trial based on a cue.

The researchers recorded signals from neurons in two different areas of the brain and found that neurons in the ventral intraparietal (VIP) area of the brain have a remarkable property: their responses to object motion change depending on the task.

That is, the neurons do not have fixed reference frames, but instead flexibly adapt to the demands of the task and change their reference frames accordingly.

Neurons in VIP will represent object motion in head-centered coordinates when the subjects are required to report object motion relative to their head. They represent object motion in world-centered coordinates when the subject was required to report object motion relative to the world.

Because the neurons have such flexible responses, this means the brain may greatly simplify the process of passing along the information it needs to guide actions.

"This is the first study to show that neurons can flexibly represent spatial information, such as object motion, in different coordinate systems based on the instructions given to the subject," DeAngelis says. "This means the brain can decode—or 'read out'—information from this single population of neurons and be able to have the information it needs for either task situation."

The VIP area is located in the parietal lobe of the brain and receives inputs from visual, auditory, and vestibular (inner ear) senses. This is the first study to test for flexible reference frames, so the VIP area is the only area known to have this property. The researchers suspect, however, that neurons in other areas of the brain may have this property as well.

Applications for neural prosthetics and brain disorders

The research offers important information about the inner workings of the brain and potentially could be used for applications such as neural prosthetics, in which brain activity is used to control artificial limbs or vehicles.

"To make an effective neural prosthetic, you want to collect signals from the brain areas that would be most useful and flexible for performing basic tasks," DeAngelis says. "If those tasks involve intercepting moving objects, for example, then tapping into signals from VIP might be a way to make a prosthetic work efficiently for a variety of tasks that would involve judging motion relative to the head or the world."

Although this research is not currently connected to a specific brain disorder, researchers have previously found that humans' ability to take in sensory information and infer which events in the world caused that sensory input—an ability known as causal inference—is impaired in disorders such as autism and schizophrenia.

"In ongoing and future work, we are studying the neural mechanisms of this causal inference process in more detail, using related tasks that involve interactions between object motion and self-motion," DeAngelis says.

Monique Mendes, Neuroscience

"As a younger black woman who wants to go into science and medicine, I don't have very many people in my life who go into my field of interest, and definitely not many who look like me, so Monique is a role model. She takes away some of the feelings of 'otherness' that I feel in certain situations and serves as a reminder that I can do this and that I do belong. I love that even though I haven't known her long, she's constantly very supportive and encouraging. Even after my time in Rochester came to an end, Monique has periodically checked on me to see how I am progressing. It speaks greatly to her character. Monique is an extremely hard worker who has a compassionate spirit that matches, if not exceeds, her brilliance as a scientist," wrote Sebrena Brink, 2018 MSTP (Medical Scientist Training Program) Summer Scholar.

Neuroscience graduate student Monique Mendes, M.S., has received the Edward Peck Curtis Award for Excellence in Teaching by a Graduate Student.

"I'm extremely proud of my students and what they have accomplished in and outside of the lab. I am incredibly fortunate to have been presented with opportunities to teach students throughout my Ph.D. I want to thank them because I have learned so much in the process," Mendes said.

Mendes was one of 13 graduate students to be honored with this award, which requires graduate students to have significant interaction with undergraduate students in the classroom or lab, and excel in advancing the teaching mission of the University by providing highly-skilled and innovative instruction.

"I was thoroughly convinced by the nomination submitted by the faculty that Monique is an outstanding educator with a bright future," Vice Provost and University Dean of Graduate Education Melissa Sturge-Apple, Ph.D., said. In presenting the award to Mendes virtually earlier this month, Sturge-Apple presented Mendes remarked "I'm grateful for all of your hard work and your mentoring and teaching which is central to the mission of our University, so I was so honored to give you this award. I wish I could do it in person."

During the presentation, Sturge-Apple read some of the nomination letters considered in the process:

"She [Monique] has a very didactic nature to her that is beautiful complimented by her enthusiasm and her vigor. She sets the setting naturally and her persistent work ethic is taught without words but through actions."

"As a younger black woman who wants to go into science and medicine I don't have very many people in my life who go into my field of interest and definitely not many who look like me, so Monique is a role model in that sense as well. She takes away some of the feelings of otherness that I had in certain situations and serves as a reminder that I can do this and I do belong."

"She has a passion that's contagious and she is clear and succinct in conveying information. She wants those around her to understand the material and to love it the same way that she does."

Mendes is a 5th year student in the Neuroscience Graduate Program and is studying the dynamics and kinetics of microglia self-renewal in the adult brain.

Rianne Stowell, Ph.D. was awarded the Wallace O. Fenn Award for her thesis that characterizes the dynamics of microglia, and the mechanisms regulating the function of these cells in different areas of the brain. This award is given annually to a graduating student who has performed especially meritorious research. According to her advisor Ania Majewska, Ph.D., the research that contributed to Stowell's thesis was published in a series of three manuscripts and two reviews. Stowell's work put microglia in the spotlight, as heterogeneous complex cells that are exquisitely tuned to activity in the brain. One of the main ¬- ¬and surprising - findings was that their activities are largely carried out in the quiescent or sleeping brain. This discovery has broad implications for understanding how microglia fit into the functions of the brain's networks and the development of novel therapeutics for neurological diseases where microglial function is likely altered. "The work highlights Stowell's strong independent streak and a great work ethic," Majewska said. "That, coupled with her innate intellectual abilities and creativity, results in a winning combination that will take her far in the future. This thesis is a great beginning to an incredibly promising scientific journey."

Dawling Dionisio-Santos, M.D., Ph.D. was awarded The Vincent du Vigneaud Award for his thesis work that was judged as superior and unique with the potential to stimulate and extend research in the field. According to Dionisio-Santos' advisor M. Kerry O'Banion, M.D., Ph.D., Dionisio-Santos moved his research in a more translational direction and initiated a series of experiments using glatiramer acetate, a drug currently prescribed for the treatment of multiple sclerosis. He discovered that, in addition to reducing amyloid plaque levels, glatiramer acetate also reduces tau pathology and improves behavioral performance, demonstrating clear translational relevance for patients with Alzheimer's disease. "Dionisio-Santos is a talented future physician-scientist," O'Banion said. "With outstanding potential based on his demonstrated ability to carry out complex experiments and analyses, develop new ideas and experiments based on thorough evaluation of the literature, and inspire others with his passion for wanting to better understand neurodegenerative diseases."

A new study shows that when specific human brain cells are transplanted into animal models of multiple sclerosis and other white matter diseases, the cells repair damage and restore function. The study provides one of the final pieces of scientific evidence necessary to advance this treatment strategy to clinical trials.

"These findings demonstrate that through the transplantation of human glial cells, we can effectively achieve remyelination in the adult brain, " Steve Goldman, M.D., Ph.D., professor of Neurology and Neuroscience at the University of Rochester Medical Center (URMC), co-director of the Center for Translational Neuromedicine, and lead author of the study. "These findings have significant therapeutics implications and represent a proof-of-concept for future clinical trials for multiple sclerosis and potential other neurodegenerative diseases."

The findings, which appear in the journal Cell Reports, are the culmination of more than 15 years of research at URMC understanding support cells found in the brain called glia, how the cells develop and function, and their role in neurological disorders.

Goldman's lab has developed techniques to manipulate the chemical signaling of embryonic and induced pluripotent stem cells to create glia. A subtype of these, called glial progenitor cells, gives rise to the brain's main support cells, astrocytes and oligodendrocytes, which play important roles in the health and signaling function of nerve cells.

Games with one vote:

• Agricola
• Axis and Allies
• Balderdash
• Betrayal at Baldur's Gate
• Blokus
• Cany Land
• Captain Sonar
• Chutes & Ladders
• Dinosaur Island
• Elder Sign
• Exploding Kittens
• Go
• Guess Who
• Jenga
• King of Tokyo
• Labyrinth
• Oh Hell
• Parcheesi
• Puerto Rico
• Scattergories
• Secret Hitler
• Sequence
• Shadows over Camelot
• Snakes and Ladders
• Superfight
• Taboo
• Top Secter Spies
• Trivial Pursuit
• Trouble
• Zombicide

Congratulations to our four outstanding graduates. Your dedication and hard work have paid off. Meliora!

• Aimee Morris, M.D., Ph.D.
• Dawling Dionisio-Santos, M.D., Ph.D.
• Jessica Hogestyn, Ph.D.
• Rianne Stowell, Ph.D.