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Krishnan Padmanabhan has publication in Frontiers in Computational Neuroscience
Monday, July 13, 2020
Top-Down Control of Inhibitory Granule Cells in the Main Olfactory Bulb Reshapes Neural Dynamics Giving Rise to a Diversity of Computations
Growing evidence shows that top-down projections from excitatory neurons in piriform cortex selectively synapse onto local inhibitory granule cells in the main olfactory bulb, effectively gating their own inputs by controlling inhibition. An open question in olfaction is the role this feedback plays in shaping the dynamics of local circuits, and the resultant computational benefits it provides. Using rate models of neuronal firing in a network consisting of excitatory mitral and tufted cells, inhibitory granule cells and top-down piriform cortical neurons, we found that changes in the weight of feedback to inhibitory neurons generated diverse network dynamics and complex transitions between these dynamics. Changes in the weight of top-down feedback supported a number of computations, including both pattern separation and oscillatory synchrony. Additionally, the network could generate gamma oscillations though a mechanism we termed Top-down control of Inhibitory Neuron Gamma (TING). Collectively, these functions arose from a codimension-2 bifurcation in the dynamical system. Our results highlight a key role for this top-down feedback, gating inhibition to facilitate often diametrically different computations.Read More: Krishnan Padmanabhan has publication in Frontiers in Computational Neuroscience
URMC Tapped to Advance Research in Intellectual and Developmental Disabilities
Wednesday, July 8, 2020
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.Read More: URMC Tapped to Advance Research in Intellectual and Developmental Disabilities
Study: Neurons can shift how they process information about motion
Friday, June 19, 2020
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.Read More: Study: Neurons can shift how they process information about motion
‘Time is vision’ after a stroke
Wednesday, May 27, 2020
A research team including professor of ophthalmology Krystel Huxlin (right, in a 2019 photo) provided stroke patients with a form of physical therapy for the visual system using a device Huxlin developed. (University of Rochester photo / J. Adam Fenster)
A person who has a stroke that causes vision loss is often told there is nothing they can do to improve or regain the vision they have lost.
But research from the University of Rochester, published in the journal Brain, may offer hope to stroke patients in regaining vision.
The Rochester team found that survivors of occipital strokes—strokes that occur in the occipital lobe of the brain and affect the ability to see—may retain some visual capabilities immediately after the stroke, but these abilities diminish and eventually disappear permanently after approximately six months. By capitalizing on this initial preserved vision, early vision training interventions can help stroke patients recover more of their vision loss than if training is administered after six months.
“One of our key findings, which has never been reported before, is that an occipital stroke that damages the visual cortex causes gradual degeneration of visual structures all the way back to the eyes,” says Krystel Huxlin, the James V. Aquavella, MD Professor in Ophthalmology at the University of Rochester’s Flaum Eye Institute.
The Rochester research team—including Elizabeth Saionz, a PhD candidate in Huxlin’s lab and the first author of the paper; Duje Tadin, professor and chair of the Department of Brain and Cognitive Sciences; and Michael Melnick, a postdoctoral associate in Tadin and Huxlin’s labs—also discovered that early intervention in the form of visual training appears to stop the gradual loss of visual processing that stroke victims may experience.
Vision stroke rehabilitation remains a developing field, and previous studies and trials of experimental therapies have focused on patients with chronic vision loss—that is, patients who are more than six months post-stroke.
“Right now, the ‘standard of care’ for vision stroke patients is that they don’t receive any targeted therapy to restore vision,” Saionz says. “They might be offered therapy to help maximize use of their remaining vision or learn how to navigate the world with their new limited vision, but there are no treatments offered that can give them back any of the vision that they lost.”
The new study compared chronic patients—those who were more than six-months post-stroke—with early subacute patients, who started training within the first three months after their stroke.
The researchers trained both groups of stroke patients using a computer-based device Huxlin developed. The training is a form of physical therapy for the visual system and involves a set of exercises that stimulates undamaged portions of the visual cortical system to use visual information. With repeated stimulation, these undamaged parts of the brain can learn to more effectively process visual information that is not filtered by the damaged primary visual cortex, partially restoring conscious visual sensations.
The researchers discovered that the subacute patients who underwent such vision training recovered global motion discrimination—the ability to determine the direction of motion in a noisy environment—as well as luminance detection—the ability to detect a spot of light—faster and much more efficiently than the chronic patients.
Overall, the group’s findings suggest that individuals may maintain visual abilities early after a stroke, indicating they have preserved some sensory information processing that may temporarily circumvent the permanently damaged regions of the brain. Early visual training may therefore be critical both to prevent vision from degrading and to enhance restoration of any preserved perceptual abilities.
“For the first time, we can now conclusively say that just as for sensorimotor stroke, ‘time is vision’ after an occipital stroke,” Huxlin says.
The study was funded by the National Institutes of Health, including NIH’s National Center for Advancing Translational Sciences and National Institute of General Medical Sciences, as well as the Research to Prevent Blindness Foundation.Read More: ‘Time is vision’ after a stroke
NGP Student Honored with Edward Peck Curtis Award for Excellence in Teaching
Friday, May 22, 2020
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.
Two 2020 NGP Graduates Honored for Thesis Work
Friday, May 22, 2020
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.”
Maiken Nedergaard honored by American Stroke Association for dedication to stroke research
Monday, February 24, 2020
Maiken Nedergaard, M.D., D.M.Sc., co-director of the Center for Translational Neuromedicine, professor in the Departments of Neurology, Neuroscience and Neurosurgery, received the Thomas Willis Lecture Award from the American Stroke Association. The award honors Nedergaard’s career of significant contributions to the basic science of stroke research.
The Nedergaard lab is dedicated to deciphering the role of neuroglia, cell types that constitute half of the entire cell population of the brain and spinal cord.
Last month, the lab published research showing that during a stroke the glymphatic system goes awry, triggers edema and drowns brain cells. In 2012, Nedergaard and her colleagues first described the glymphatic system, a network that piggybacks on the brain’s blood circulation system and is comprised of layers of plumbing, with the inner blood vessel encased by a ‘tube’ that transports cerebrospinal fluid (CSF). The system pumps CSF through brain tissue, primarily while we sleep, washing away toxic proteins and other waste.
The Thomas Willis Award honors the prominent British physician credited with providing the first detailed description of the brain stem, the cerebellum and the ventricles, with extensive hypothesis about the functions of these brain parts. The award recognizes contributions to the investigation and management of stroke basic science.
Nedergaard was one of eleven leading scientists honored for their work by the American Stroke Association. The awards were given during the American Stroke Association’s International Stroke Conference in Los Angeles.
Suzanne Haber Honored by Society of Biological Psychiatry for Research on Mental Disorders
Thursday, January 30, 2020
Suzanne N. Haber, Ph.D., Dean’s Professor in the Department of Pharmacology and Physiology, will receive the Society of Biological Psychiatry’s 2020 Gold Medal Award at the Society’s 75th Annual Scientific Convention & Meeting in the spring. The award honors members of the Society whose significant and sustained work has advanced and extended knowledge on the neurobiology of mental illness.
Haber’s lab investigates the cortico-cortical and cortico-basal ganglia systems in the brain. Her work demonstrates the specific hard-wired connections that are associated with normal decision making, emotional and cognitive control, and the connectional abnormalities in those circuits that are linked to a wide range of mental health disorders, including obsessive-compulsive disorder (OCD), drug abuse and addiction, schizophrenia, and motor control disorders such as Parkinson’s disease. This work has played a key role in targeting and interpreting the effects of noninvasive and invasive therapeutic approaches for OCD and depression.
For the past ten years, Haber has led the Silvio O. Conte Center for Basic and Translational Mental Health Research at the University of Rochester. Funded by the National Institute of Mental Health, the Center uses translational approaches to probe the neurocircuitry that underlies neuromodulation for OCD, pinpointing specific abnormalities within the brain circuits that are associated with the disease. This information is being used to guide new treatment options for the three million-plus Americans who live with the disorder.
“Suzanne’s seminal contributions to elucidating specific neural networks that control learning, decision-making, reward and motivation, and how pathologies associated with these neural communication hubs underlie multiple neurological, movement, and mental health disorders make her uniquely qualified to receive this prestigious career award,” said Robert T. Dirksen, Ph.D., Lewis Pratt Ross Professor and Chair of the Department of Pharmacology and Physiology. “Her work is making a difference in the lives of individuals and families suffering from neurological and mental health disorders. We are extremely proud that she represents the University of Rochester as a Society of Biological Psychiatry Gold Medal Award winner.”
The Society of Biological Psychiatry was founded in 1945 to emphasize the medical and scientific study and treatment of mental disorders. It’s the oldest neuropsychiatry research society in America, currently made up of more than 1,500 members from across the United States, Canada, Europe and Asia. Members conduct research in areas spanning from basic cellular studies to clinical trials and prevention research.
Haber, who is also a professor of Neuroscience, Brain and Cognitive Science, and Psychiatry, will split the 2020 Gold Medal Award with Carol Tamminga, M.D. of UT Southwestern Medical Center.