NeURoscience Newsletter | Vol 18 | 2023

NE UR OSCIENCE

Protecting the vulnerable, informing the future

How an unlikely team kept students with severe and complex disabilities safe and in school PG

John J. Foxe, PhD

FROM THE DIRECTOR’S DESK

This issue, particularly our cover story, may seem a little different, and that’s because it is. I’ve been looking forward to sharing this work with our readers because it showcases what a strong multidisciplinary community like ours can do in a time of great need, even if the task is unlike anything we had ever been confronted with before.

right time, paving the way to make this project possible.

Professor & Chair, Department of Neuroscience

The NIH-funded project, RADx-UP, short for “Rapid Acceleration of Diagnostics in Underserved Populations,” coalesced a team of faculty, staff, and leadership, from an array of backgrounds and expertise, to tackle one of the great challenges of our era. How do we keep children with severe intellectual and developmental disabilities and complex medical needs safe and in school as a pandemic rages? You will learn how an unlikely team came together to find solutions and how our partnership with the extraordinary people at the Mary Cariola Center has allowed us to inform national policy. It is a project we unknowingly spent years preparing for, and it is one that has left a considerable mark on all of us.

I’m grateful that the NIH designation of our University of Rochester Intellectual and Developmental Disabilities Research Center (UR-IDDRC) came at just the

ON THE COVER:

Del Monte Institute for Neuroscience Executive Committee

John Foxe, PhD, Chair, Department of Neuroscience

Bradford Berk MD, PhD, Professor of Medicine, Cardiology

Robert Dirksen, PhD, Chair, Department of Pharmacology & Physiology

Diane Dalecki, PhD, Chair, Department of Biomedical Engineering

Jennifer Harvey, MD, Chair, Department of Imaging Sciences

Robert Holloway, MD, MPH, Chair, Department of Neurology

Our faculty has had another prolific few months. As you read on, discover the new advances in neuroscience that are shaping our understanding of eye-andhand coordination and neuropsychiatric disorders in teens. Our scientists have also created one of the most detailed 3D images of the synapse—the junction where neurons communicate with each other through an exchange of chemical signals. This 3D technology could transform our understanding of what happens at these connections.

This summer marks year three of the Neuroscience Diversity Commission’s NEUROCITY program. Nine undergraduate students from City College New York are working in our neuroscience labs this summer. We are grateful for the warm welcome and hospitality bestowed on them in their early days in Rochester as they were welcomed to the home of the President of the University for a picnic (see back cover). In Science,

John J. Foxe, PhD

Paige Lawrence, PhD, Chair, Department of Environmental Medicine

Hochang (Ben) Lee, MD, Chair, Department of Psychiatry

Shawn Newlands, MD, PhD, MBA, Chair, Department of Otolaryngology

Webster Pilcher, MD, PhD, Chair, Department of Neurosurgery

Steven Silverstein, PhD, Professor, Department of Psychiatry

Duje Tadin, PhD, Chair, Department of Brain & Cognitive Sciences

NEUROSCIENCE

Editor/Writer

Kelsie Smith Hayduk Kelsie_Smith-Hayduk@ urmc.rochester.edu

Contributors

Mark Michaud, Jim Miller

Feature Photography John Schlia Photography

Designer Beth Carr

Kilian J. and Caroline F. Schmitt Chair in Neuroscience

Director, Ernest J. Del Monte Institute for Neuroscience

Deb Knickerbocker, Teacher on Special Assignment, pushes a student on a swing outside of the Mary Cariola Center in Rochester.

Research continues to rule out brain’s immune system as key to fetal alcohol spectrum disorders

Researchers found early alcohol exposure does not change the connection between the brain's immune system and neurons that send information related to functions like balance and memory. In the Majewska Lab at the Del Monte Institute for Neuroscience at the University of Rochester, researchers investigated the interaction between microglia and Purkinje neurons—the neurons responsible for sending information from the cerebellum. Published in Frontiers in Neuroscience their research found that mice exposed to ethanol during development had no differences in microglia movement or structure and only subtle changes in the interaction between microglia and Purkinje neurons.

The Majewska lab’s research initially poked holes in the idea that FASD is driven by damage caused in the brain by impaired microglia when it found no difference in microglia activity in the brains of mice exposed to alcohol early in development when compared to those who were not exposed.

One out of every 100 babies born in the U.S. is diagnosed with FASD, which occurs when a child is exposed to alcohol in the womb. Currently, there is no available treatment.

Researchers find possible target for treating neuropsychiatric disorders in teens

The onset of neuropsychiatric disorders like schizophrenia often begins during young adulthood. Dysfunction of the dopamine system—necessary for cognitive processing and decision-making— begins during this point in development. Researchers in the Wang Lab at the Del Monte Institute for Neuroscience at the University of Rochester are coming closer to finding a possible target for treating neuropsychiatric disorders like schizophrenia and autism during this time of development that could affect the brain circuitry into adulthood.

By targeting underperforming neurons in the dopamine system that connect to the frontal cortex in mice, researchers found that they could strengthen this circuit and rescue structural deficiencies in the brain that cause long-term symptoms. This research, published in the journal eLife, suggests that increasing the activity of the adolescent dopaminergic circuitry can rescue existing deficits in the circuit and be long-lasting as these changes persist into adulthood.

Research finds prediction may be key to eye-and-hand coordination

Have you ever made a great catch—like saving a phone from dropping into a toilet or catching an indoor cat from running outside? Those skills—the ability to grab a moving object—take precise interactions within and between our visual and motor systems. Researchers in the Wang lab at the Del Monte Institute for Neuroscience at the University of Rochester have found that the ability to visually predict movement may be an important part of the ability to make a great catch or grab a moving object.

The research, published in Current Biology, used multiple high-speed cameras and DeepLabCut—an AI method that uses video data to find key points on the hand and arm to measure movements—to record where the primate is looking and the movement of the arm and hand as it reaches and catches moving crickets. Researchers found an 80-millisecond delay in the animal’s visuomotor behavior—the moment when vision and movement click and work together to direct the hand toward the target. Despite this measurable delay, the primates still grabbed the crickets, meaning that it had to predict the cricket’s movement. Using data of both the primates and the crickets the researchers were able to build a detailed model of vision-guided reaching behavior.

A chance observation finds potential hearing biomarker for Alzheimer’s disease

A Neuroscience graduate student in the White Lab at the Del Monte Institute for Neuroscience at the University of Rochester was reviewing data for one project but instead discovered that the location of plaques associated with Alzheimer’s disease in the brain may contribute to hearing loss. During hearing tests on mice with amyloid beta, the main component of protein plaques and tangles found in Alzheimer’s, the student found that for one model, called 5xFAD, the older mice had hearing changes similar to what is found in people with Alzheimer’s disease. The other model did not demonstrate these hearing changes, nor did younger mice in the 5xFAD group.

The research, published in Frontiers in Neuroscience, found that the brains of older mice from both models had plaques in the hippocampus and auditory cortex. But the brains of mice with hearing changes also had a small amount of plaque on the auditory brainstem, suggesting this area may be sensitive to disruption from plaque found in Alzheimer’s. Researchers discovered that the plaque reduced the brainstem’s ability to coordinate responses to sound.

AI helps show how the brain's fluids flow

A new artificial intelligence-based technique for measuring fluid flow around the brain’s blood vessels could have big implications for developing treatments for neurological conditions including Alzheimer’s, small vessel disease, strokes, and traumatic brain injuries. The perivascular spaces that surround cerebral blood vessels transport water-like fluids around the brain and help sweep away waste.

A multidisciplinary team of mechanical engineers, neuroscientists, and computer scientists led by University of Rochester Associate Professor Douglas Kelley, PhD,  developed novel AI velocimetry measurements to accurately calculate brain fluid flow. The results are outlined in a study published by Proceedings of the National Academy of Sciences. This technique allowed researchers to effectively measure things that have not been measured before.

New images capture unseen details of the synapse

Scientists have created one of the most detailed 3D images of the synapse, the juncture where neurons communicate with each other through an exchange of chemical signals. These nanometer scale models will help scientists better understand and study neurodegenerative diseases such as Huntington’s disease and schizophrenia.

The study appears in the journal PNAS and was authored by a team led by Steve Goldman, MD, PhD, co-director of the Center for Translational Neuromedicine at the University of Rochester and the University of Copenhagen. The findings represent a significant technical achievement that allows researchers to study the different cells that converge at individual synapses at a level of detail not previously achievable, and holds the potential to advance our understanding of neurodegenerative and neuropsychiatric diseases in which synaptic function is disturbed.

Q&A with Lars A. Ross, PhD

Lars A. Ross, PhD, is a research assistant professor of Imaging Sciences and Neuroscience at the University of Rochester Medical Center. He received a graduate degree in psychology at Humboldt University in Berlin, Germany, and completed his PhD in the cognitive neuroscience program at The City College of New York. He went on to do postdoctoral research at Temple University and University of Pennsylvania. He came to URMC in late 2020, and his research aims to understand how information from our senses is integrated and processed in the brain and how this impacts perception, cognition, and behavior. He is also interested in how these processes develop throughout life and differ in neurodevelopmental disorders such as autism.

Please tell us about your research.

I am interested in how information from different sensory modalities is integrated in the brain, also called multisensory integration, and the effect it has on perception, cognition, and behavior. Most of my work is in audiovisual speech perception, studying the effect of visual articulation on speech recognition.

I am also interested in how these important brain functions develop throughout childhood and into adulthood, and I explore differences in neurodevelopmental disorders such as autism. I have used psychophysics, electroencephalography,

and transcranial direct current stimulation in my studies but in recent years I have mostly been conducting behavioral experiments and neuroimaging.

How did you become interested in your area of expertise?

I actually came to the US initially to study sleep and sleep disorders but ended up joining a fellowship program in developmental neuroscience with a researcher who studied multisensory integration in babies and toddlers. At that time, I was working on an experiment using a multisensory motion illusion when I discovered that John Foxe’s team was working with the same paradigm with the addition of doing electrophysiological recordings in humans. I had done EEG work for my graduate degree in Psychology in Berlin and was very interested in deepening my skills and knowledge of this technique. It was through that common interest that we began our work together and I eventually became his PhD student with multisensory integration as the focus of my dissertation.

What brought you to the University of Rochester?

It was brought to my attention that the Imaging Sciences Department was looking for a researcher who would also help them with perfusion post processing, a relatively novel technique in neuroimaging that is used to diagnose brain tumors. The idea of doing something new that had a direct clinical application appealed to me and now my work is split between Imaging Sciences and Neuroscience. I am also happy to be back in the lab where I completed my PhD.

What is your favorite piece of advice? So what?

Here is a quote from Andy Warhol:

“Sometimes people let the same problem make them miserable for years when they could just say, “So what?, I don’t know how I made it through all the years before I learned how to do that trick. It took a long time for me to learn it, but once you do, you never forget.”

I like this “advice” for its radical simplicity and broad applicability. I just wish it was easier to follow.

Lars A. Ross, PhD

Protecting the vulnerable,

How an unlikely team kept students with severe and complex disabilities safe and in school

This is not another story about COVID. This is a story about how a group of scientists—including a neuroscientist, virologist, and nephrologist—and school leadership rolled up their sleeves, stepped outside of their comfort zones, and formed an unlikely team that relentlessly navigated a pandemic in real-time to keep some of the most vulnerable students to the virus safe, staff healthy, schools open, and how at times, they were able to stop COVID in its tracks.

COVID WAS LEADING CAUSE OF DEATH FOR PEOPLE WITH INTELLECTUAL AND DEVELOPMENTAL DISABILITIES (IDD) IN 2020

According to a study in the journal of Disability and Health, COVID was the number one cause of death in individuals with an IDD in 2020.

According to the NIH, a non-vaccinated person with an IDD is four times more likely to contract COVID-19 and eight times more likely to die from the virus than someone without an IDD.

A national designation

In April 2020, as COVID wreaked havoc across the globe, the University of Rochester received a new designation from the National Institutes of Health (NIH). It became one of about a dozen Intellectual and Developmental Disabilities Research Centers (IDDRC) in the country. This designation makes the University one of only eight with the “trifecta” of NIH awards related to intellectual and developmental disabilities (IDD), which includes the established University Centers for Excellence in Developmental Disabilities Education, Research, and Service (UCEDD), with its focus on training and service; and Leadership Education in Neurodevelopmental and Disabilities (LEND) program, with a focus on education.

This newly minted designation strengthened the long-standing relationship between the Neuroscience community at the University and the Mary Cariola Center that dates back to Tris Smith, PhD, a pioneer in autism research who helped cultivate that connection and build part

Steve Dewhurst, PhD

informing the future

of the foundation for the UR-IDDRC before his untimely passing in 2018. So, a year into the pandemic, when the NIH was looking to understand how COVID was spreading in the IDD population, the UR-IDDRC and Mary Cariola took on a $4 million project, funded by the NIH Rapid Acceleration of Diagnostics-Underserved Populations (RADx-UP) program.

“Very few IDDRCs could have done what we were able to do in this project. This strong relationship [between UR and the Mary Cariola Center] has been built up over years, and is founded on mutual respect and trust. The underlying maxim that John Foxe and others continually reinforce is: “nothing about us, without us”—which defines a best practice when partnering with historically marginalized populations,” said Steve Dewhurst, PhD, vice dean of research at the Medical Center, recently named vice president for research at the University, and co-principal investigator of the RADx-UP study. “That coupled with the size of our academic Medical Center, we are small enough that we know each other but diverse enough that we could create this team that included me, a virologist, the senior associate dean of clinical research [Zand], and the co-director of the IDDRC [Foxe]. Then to have a testing lab already up and running and highly trained staff in the school, we were the right place for this to happen.”

“If there is a group of students that cannot afford to miss being in school, it is this group,” said John Foxe, PhD, director of the Del Monte Institute for Neuroscience, co-director of the UR-IDDRC, and co-principal investigator of the RADx-UP

study. “Many children with an IDD have social communication deficits, speech, and complex health or medical issues. These students need intensive sensory interaction, intervention, and as much socialization and social interaction as we can give them. They need to be in school.”

From left: Ed Freedman, PhD, led of the testing team and John Foxe, PhD.

From left: Martin Zand, PhD, and Christopher Seplaki, PhD.

Andrew Cameron, PhD, D(ABMM), assistant director of Clinical Microbiology Laboratories at URMC. The lab performed 16,000 COVID tests as part of the RADx-UP study.

COVID testing was the key

“We could not get testing, and it’s what we needed to keep our schools open,” said Karen Zandi, president, and CEO of the Mary Cariola Center. The Center serves more than 450 students ages 3-21 with severe IDDs and complex medical needs. When Zandi learned this project would bring testing into their schools and take the burden off staff and students, she saw it as a necessary opportunity. “[This partnership] allowed us to offer testing onsite, and, eventually, it provided mobile testing. There was a

trust factor for many of our families about where and who was administering the test. Many were grateful we could do it right at school.”

wanted to do my part in keeping my family, grandkids, friends, and coworkers safe. I continued to stay in the study and to be tested weekly so I would be able to know if I had COVID to keep the students in my classroom safe.”

Preventing the spread of an airborne virus can prove difficult in a population of people who do not understand social distancing and, in many cases, cannot wear or tolerate a mask. But like all schools, they adjusted to meet requirements and mandates. They altered classroom environments, added plexiglass shields, and bought more equipment to keep the students from sharing. And when the testing came into the building, so did the real-time benefits.

“Almost immediately, we were able to catch positive cases early and identify asymptomatic people as well,” said Zandi.

Karen Zandi (right) interacts with a Mary Cariola student at their East Avenue campus in Rochester.

From left: Sam Spallina, Alex Solorzano, and Davida Rogers conducted testing at Mary Cariola. They also used the van, in the background, to provide mobile testing.

“Ienrolled in the COVID study because I

– Lisa Prince, Teacher Aid II, Mary Cariola Center

From left, Prince and Solorzano in testing room at Mary Cariola Center.

Achieving herd immunity

Isolating persons with positive tests and knowing antibody levels within the Mary Cariola Center community helped keep the virus at bay. Vaccinations were not given or required in this research project, but antibody levels—from vaccinations and illness—were collected and considered as the school reacted to an ever-changing environment. “We could see how the immunity progressed and changed in both vaccinated and unvaccinated people within the study,” said Martin Zand, MD, PhD, co-director of the Clinical & Translational Science Institute and co-principal investigator of the RADx-UP project, who leads this aspect of the research, including collecting the samples at the school. “Because of this, we know we achieved herd immunity at the school.”

With this data, coupled with COVID tests, and other information specific to the school, Zand and Christopher Seplaki, PhD, associate professor of Public Health Sciences, created hundreds of models(scenarios) to understand how an airborne virus could travel through the buildings, hallways, and

classrooms. “These models informed us how we might help school officials lessen the burden of a respiratory disease that arises in the community,” said Zand. “Keeping these students safe was the highest priority. The staff were curious as to whether the things they were doing were benefiting the people in the school. Everyone on the team was curious. We all taught each other.”

“We have been very happy that we enrolled Harry in the study. He has become so comfortable with having the testing done and we are hoping this will carry over to other medical procedures. It has been wonderful for Harry and our family to get to know some of the people involved in the study, as well! We feel good knowing Harry is contributing to the database and helping his community, and it’s great knowing he will be checked regularly so we can have extra eyes on his health.”

– Sarah Tedesco, Parent of Cariola Student

Success means remaining quick and nimble

Every Wednesday morning, nearly a dozen people meet over Zoom. These regular meetings started in 2021 and allowed the team to respond quickly and adjust to the fluidity of studying an evolving virus within a school. The translational nature of this project meant that as testing came in, models considered different scenarios, and in these meetings, both the school officials and the scientists could ask and answer questions in real-time. “It was fascinating how the study evolved,” said Ann Dozier, PhD, chair of Public Health Sciences, co-investigator, and lead of community engagement for the project. “There are very senior people on this project, like John, Steve, and Martin. They were key in helping to navigate it. Discussions and adjustments to new strains and mandates were all part of those weekly meetings.”

“We had a lot less missed [staff and student] time due to illness than we would have had without this study. The availability of testing was vital because everybody was frightened about the virus. The rule was, you do not feel well, stay home,” Zandi said. “But because of RADx-UP, we give tests and get immediate results. We were able to ease some of the

burdens for our staff and parents who wondered if they should or could send their child to school. It was a lot of information, constant work, and communication, but it worked well with our nurse who managed this with our medical team and the Medical Center testing team.”

Informing the future: Airborne illnesses in the IDD community

The data collected by this study could change how organizations respond to airborne viruses in settings that support the IDD community in the future. The team has shown that protocols and procedures can mitigate the spread of COVID. “We are working on the datasets and are starting to tee up a series of publications about our observations,” Foxe said. “We wanted to see the whole picture and use dense data over a long period to be able to say something substantive to be used to help keep this vulnerable population safe.”

Keeping the students safe is why both people at URMC and the Mary Cariola Center raised their hands to take on this project. That shared mission is on track to having broad, lifesaving implications. “You’re not getting past the door unless you love the Cariola students first. They are an important part of our community with lots of gifts and ability,” Zandi said. “The people involved in the study demonstrated that their work kept our students and staff safe and will provide fruitful information to others living and working in the IDD community on how they can mitigate the spread of airborne viruses. From my perspective, testing was a very important part.”

From left: Anne Francis, MD, medical director and Anne Pawlowski, RN, nurse manager of the Mary Cariola Center, were instrumental helping organize onsite testing and responding to real time results.

Ann Dozier, PhD

Allison Murphy, PhD

Allison Murphy, PhD (’23), a postdoctoral associate in the lab of Farran Briggs, PhD, received a doctoral degree in Neuroscience from the University of Rochester School of Medicine and Dentistry. Her research focuses on the structure and function of a feedback connection between two brain areas: the primary visual cortex and the visual part of the thalamus (LGN). Examining how this connection is organized, and how the neurons in the primary visual cortex influence the activity in the LGN could aid in understanding how this pathway contributes to visual processing.

“When people think about vision, they often think about the eyes, but a huge part of the brain is part of the visual processing system,” said Murphy. “There is this information loop between the visual cortex and LGN that we do not fully understand. A big part of my thesis research involved figuring out why this circuit exists and the role it plays in our vision.”

Murphy completed her undergraduate degree at Denison University. She majored in Biology with a concentration in Neuroscience. It was during that time she became interested in visual neuroscience.

The storied history of vision science at the University of

Neuroscience Legacy Series welcomes John Kruse, ’82, ’89M (PhD), ’90M (MD)

John Kruse, MD, PhD, kicked off the Neuroscience Legacy Series in April. He met with both faculty and students to share more about his professional journey. Kruse is a renowned expert on Attention Deficit Hyperactivity Disorder (ADHD).

Rochester School of Medicine and Dentistry, including the Center for Visual Science, made Rochester her first choice for graduate school.

Long term, Murphy plans to continue to study vision neuroscience. “I find the link between the activity in our brain and our visual experience really interesting. We still don’t fully understand how all of these brain areas work together to help us see, so there are many exciting areas of research to pursue in the future.”

Allison Murphy, PhD

2023 Del Monte Ins�tute & UR-IDDRC Symposium

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WELCOME TO ROCHESTER!

June 2023: This year’s cohort of NEUROCITY scholars and Meliora and BilskiMayer summer research students in the Brain and Cognitive Sciences Department (BCS) at the University of Rochester gathered for a welcome picnic at the University of Rochester Witmer House. The NEUROCITY scholars from City College New York are part of the summer undergraduate pathway program supported by the Del Monte Institute for Neuroscience Diversity Commission. This is the third summer of the program. The Commission & BCS thank University of Rochester President Sarah Mangelsdorf, PhD, and her husband Karl Rosengren, PhD, for welcoming the scholars to the Witmer House.