UCSF Chancellor Sue Desmond-Hellmann, center, attends the May 3 groundbreaking ceremony of the neurosciences building to be constructed at UCSF Mission Bay.
Nobel laureate Stanley Prusiner, director of UCSF’s Institute for Neurodegenerative Diseases, was among those to speak at the symposium.
Translating Research into Treatments“This is a wonderful day,” said Steven Hauser, MD, chair of the Department of Neurology. “What we hope to accomplish in this new building is a bit audacious and extraordinarily exciting. We can bring together neuroscientists, clinical scientists and clinicians treating patients to understand how a healthy brain works, and what goes wrong when it becomes diseased.”
Stephen Hauser, chair of the Department of Neurology, says the new building will bring together “neuroscientists, clinical scientists and clinicians treating patients to understand how a healthy brain works, and what goes wrong when it becomes diseased.”
Applying Basic Research ToolsThe Keck Center’s director, Steven Lisberger, PhD, said that Keck Center scientists apply basic research tools to understand how the brain works, generates behavior and learns. He described the brain as a powerful “learning machine,” with intricate networks of neural circuits as the wiring. Electrical and chemical activity at the synapses between two neurons make the key connections, and “the strength of learning depends on the strength of those connections.” The amount of learning one is capable of – the brain’s plasticity – decreases with age, Lisberger explained. Children’s brains are fantastic learners, he said. Synapses in a growing child’s brain turn on at distinct, critical periods for different skills. He described groundbreaking research recently reported by UCSF faculty scientists Michael Stryker, PhD and Arturo-Alvarez Buylla, PhD, demonstrating in mice for the first time that a specific type of immature neuron from embryonic mice could be transplanted into the visual cortex of young mice to prompt a new period of plasticity. The finding promises a way to treat neural circuits disrupted by abnormal fetal or postnatal development, stroke, traumatic brain injury, psychiatric illness and aging. This is an exciting “proof of principle” Lisberger said. “We are poised,” he stressed, “to harness the brain’s learning abilities as medicine.” Allison Doupe, MD, PhD, studies how the brain learns or fails to learn, and how this affects development. A professor of psychiatry, she leads research in the Keck Center on neuron circuits, known as cortical-basal ganglia circuits, critical to producing sequences – such as movement, speech or thoughts. Because they are important to so much behavior, she said, the circuits turn out to be involved in a large number of diseases. Disruptions can cause motor problems, such as those found in Parkinson’s, or thought difficulties involved in obsessive-compulsive behaviors. Doupe’s lab is learning how these circuits affect a bird’s ability to gradually learn its species-specific song, and the findings provide insight into human diseases of the same structures. Some neuronal damage causes birds to repeatedly produce small numbers of abnormal syllables. These symptoms are similar to those of Parkinson’s disease, she said. Other types of songbird basal ganglia damage are reminiscent of Huntington’s and psychosis. Doupe expects that in the new building, the bird models of learning can inform her colleagues’ studies of human brain diseases, and vice versa. Another animal, the nematode known as C. elegans, might at first seem like an unlikely candidate to model human brain function. But this nearly microscopic creature shares hundreds of disease genes with humans. Aimee Kao, MD, PhD, an assistant adjunct professor in the Memory and Aging Center, has become adept at moving from her studies of how the worm’s neurons function to what this might reveal about human brain disease. She and her colleagues study a protein in the animals’ neurons similar to one in our brains, called progranulin. Normal cells are mortal. Some live a normal lifespan; others are damaged and die. But in either case, when they die, they must be “cleared” from the tissue by naturally occurring “engulfing” cells. Progranulin may regulate this process. Kao and her colleagues think that with too little progranulin, cells are engulfed and cleared too quickly, robbing the brain of an adequate neuron supply. And with too much progranulin present, brain cells are effectively invisible to engulfing cells, and grow aggressively – the hallmark of cancer. “The worm has given us a view of the normal function of this protein, Kao says. “We want to develop therapies that can restore the balance of progranulin in the human brain.”
Listening to the panel of researchers at the symposium, are from left, UCSF Chancellor Sue Desmond-Hellmann, UC Regent Richard Blum and Senator Dianne Feinstein.
Improving Brain ImagingBrain imaging has become dramatically more refined over the past decade, and Adam Gazzaley, MD, PhD, uses MRI brain imaging to study normal learning, as well as changes in learning caused by aging and disease. He also teams up with colleagues in search of ways to push the learning system to an optimal state. Director of UCSF’s Neurosciences Imaging Center, Gazzaley has used imaging to study the prefrontal cortex region in young and older healthy adults. The prefrontal cortex normally sends signals of what to pay attention to, and what to ignore in performing a task. He studies brain activity as people engage in a memory test. They are told what to focus on among a series of relevant and irrelevant cues. Gazzaley discovered from brain imaging that older adults are about as good as younger ones in the ability to focus on what they want to remember, but they are not as good at ignoring irrelevant information. “We found the degree to which a person can ignore irrelevant information tells how well they can recall the relevant information” – a clue to declining memory in many older adults. Gazzaley is now working with a team at Lucas Art to develop a challenging car-driving video game, trying to teach users to ignore irrelevant input to improve their abilities to remember more relevant information. Every hour, 87 people in the U.S. have a stroke. Very promising new strategies to save lives and minimize tissue damage are now in clinical trial, said Wade Smith, MD, PhD and a professor of clinical neurology. Smith is part of a team that developed a technique to essentially grab onto a clot and delicately drag it out of the carotid artery, before it reaches the brain and causes severe damage or death. Conventional wisdom holds that stroke victims must have clots cleared within hours to avoid severe damage or death. Surprisingly, Smith said, MRI brain imaging has recently revealed that some patients can be saved many hours past the current limit. He hopes improved imaging and intervention might be able to extend the window as long as 24 hours after a stroke. Beyond that, he said, is the hope of reintroducing healthy neurons into the brain. “We think we can do it,” Wade said, noting that he’s in a private race to “finish” stroke before Bruce Miller cures Alzheimer’s disease. Either way, it’s a win-win. The last person to speak at the symposium is the latest addition to the neurology team. Jonah Chan, PhD, joined the neurology faculty this year, fresh from a faculty position at USC, and earlier research as a neurobiology postdoctoral fellow at Stanford. Looking ahead to research and treatment planned for the new building, Chan said he didn’t choose San Francisco for the weather, or even the great scientists at UCSF. “It really is for the vision made possible by this community of scientists,” Chan said. “This is a true collaboration at UCSF that is second to none.”
Photos by Noah Berger
- Neurosciences Building to Take Scientific Research to the Next Level, UCSF Today, January 21, 2010
- UCSF Neuroscience Building to drive advances against brain diseases, UCSF News Release, January 21, 2010