Highlighting Yale’s Neuroscience Research

In an effort to better understand the impactful neuroscience research underway at Yale, Sen. Richard Blumenthal (D-CT) visited Yale School of Medicine (YSM) on June 26 for a tour of neuroscience laboratory facilities and a roundtable discussion with YSM researchers. His visit came at a crucial time as Congress begins making specific recommendations for the fiscal year (FY) 2025 budget, with National Institutes of Health (NIH) funding decisions of paramount importance for scientists at Yale and across the country.

One such recommendation came the very next day, June 27, when a subcommittee of the House Appropriations Committee approved a preliminary spending bill that would provide level combined funding for the NIH and the Advanced Research Projects Agency-Health (ARPA-H). But it would cut $1 billion from ARPA-H, potentially reallocating much of that funding among NIH institutes and centers. It is not clear whether some of that funding might help offset already-scheduled reductions in support for the “Brain Research Through Advancing Innovative Neurotechnologies” (BRAIN) initiative, a program that has a major impact on research done at Yale.

To go from a molecular discovery to a drug and a clinical trial takes more than 10 years, often closer to 20, and without continual and long-term support from the NIH, this kind of stuff can never happen. If funds are fluctuating year to year, things grind to a halt, and they can’t get restarted.

The BRAIN budget already decreased by $278 million in the past year from FY 2023, a drop that reduced available funding for both new and existing grants. While the subcommittee’s recommendation, which also includes a significant reorganization of NIH, is far from the last word in what is always a complicated budget process, it is a signal of uncertain times ahead.

BRAIN grants have funded the projects of many of Yale’s neuroscientists, and more budget cuts would impede the pace of their research. These reductions are happening during a “critical state” for neuroscience research, said Michael Crair, PhD, vice provost for research and William Zeigler III Professor of Neuroscience at YSM, during Blumenthal’s visit. “It’s just now that we’re reaching the stage of developing therapeutics for many different disorders that impact the brain, and to pull back on NIH funding right when we’re reaping the benefits of many decades of research is tragic,” Crair explained.

A tour of Yale’s neuroscience facilities

Blumenthal began the morning with a tour of the shared laboratory space of Michael Higley, MD, PhD, associate professor of neuroscience, of biomedical engineering, and of psychiatry, and Jessica Cardin, PhD, associate professor and deputy chair of neuroscience, located in the new home of the Wu Tsai Institute at 100 College St. Andrew Moberly, PhD, a postdoctoral fellow in the shared lab space, showed Blumenthal neuroimaging technologies that he and his colleagues use to track brain activity in rodents. The technology monitors electrical activity in the brain by detecting light from neurons with genetically encoded fluorescent activity indicators. This allows the researchers to see in real time which areas of the brain are being used.

Moberly is using the technology to investigate how neural activity changes in response to negative stimuli, which may provide insights into the relationship between sensory processing and behavior. He was recently awarded an NIH Pathway to Independence K99/R00 award that supports postdoctoral researchers as they transition into securing independent faculty positions, and he hopes to be able to continue his work by looking at how stress can impact sensory processing, which may be helpful for understanding conditions like post-traumatic stress disorder.

Roundtable research discussion

After touring Higley and Cardin’s laboratory, Blumenthal was joined by Nancy J. Brown, MD, Jean and David W. Wallace Dean of the Yale School of Medicine and C.N.H. Long Professor of Internal Medicine, as well as a number of YSM neuroscience research faculty, for a roundtable discussion regarding the importance of NIH funding for their work.

In addition to Crair, members of the discussion included Lauren Sansing, MD, MS, professor of neurology; Nenad Sestan, MD, PhD, Harvey and Kate Cushing Professor of Neuroscience and professor of comparative medicine, of genetics, and of psychiatry; Anthony Koleske, PhD, deputy dean for research (basic science), Ensign Professor of Molecular Biophysics and Biochemistry, and professor of neuroscience; Serena Spudich, MD, MA, Gilbert H. Glaser Professor of Neurology and a director of the Yale Center for Brain & Mind Health (CMBH); Stephen Strittmatter, MD, PhD, Vincent Coates Professor of Neurology and chair and professor of neuroscience; David Hafler, MD, chair and William S. and Lois Stiles Edgerly Professor of Neurology and professor of immunobiology; Kevin Sheth, MD, professor of neurology and of neurosurgery and a director of CMBH; and Christopher Pittenger, MD, PhD, Elizabeth Mears and House Jameson Professor of psychiatry and a director of CMBH.

Sestan spoke about the technology he developed to reverse ischemic damage in pig brains up to an hour after death, work that has led to the creation of a biotech company in New Haven. The project would not have been possible without funding from the BRAIN initiative, Sestan said, emphasizing the priority that the initiative places on interdisciplinary work.

Sestan went on to explain the importance of NIH funding globally, discussing how the BRAIN initiative has set an example for other countries around the world to increase their funding for neuroscience research. “It’s a geopolitical statement, almost as much as improving our health,” he stated. Blumenthal agreed with the importance of scientific world leadership and the need to prioritize interdisciplinary work.

Strittmatter discussed his research on amyloid plaques in Alzheimer’s patients, work that has progressed from basic discovery all the way to clinical trials, with the NIH providing funding at every step. The research has also led to the development of startup biotech companies, which Strittmatter says have created new jobs for Connecticut residents.

The need for NIH support

“To go from a molecular discovery to a drug and a clinical trial takes more than 10 years, often closer to 20, and without continual and long-term support from the NIH, this kind of stuff can never happen,” Strittmatter said. “If funds are fluctuating year to year, things grind to a halt, and they can’t get restarted.”

Others mentioned how NIH funding had launched and nurtured their careers in a field where job stability is often uncertain, and referred to their NIH-supported research into areas such as viral infections in the brain, new therapies for stroke and dementia patients, and community treatments for substance abuse.

“This kind of research is exciting in terms of where it can take us in improving quality of life and length of life, but it also represents the danger of a huge missed opportunity if we fail to sustain funding and investment,” Blumenthal stated. “What I’ve seen here at Yale will inspire me to work and fight for additional federal investment. It’s imperative for our nation at this moment, and every bit as important as the hundreds of billions that we’re spending on defense.”