When Amy Arnsten gives an honorary lecture this Wednesday at the Yale School of Medicine, she will remind us that great science is often built on the shoulders of giants.
Arnsten, who is professor of neuroscience and of psychiatry, is the recipient of the 2015 Goldman-Rakic Prize, established 13 years ago in memory of her Yale mentor, the world-renowned neuroscientist Patricia Goldman-Rakic. Arnsten, who is also a member of the Kavli Institute for Neuroscience, was awarded the prize by the Brain & Behavior Research Foundation at a ceremony in New York last fall. She is the first prizewinner from Yale.
Arnsten's lecture will highlight how decades of research at the Yale Medical School, beginning in the 1930s, and later transformed by Goldman-Rakic, is leading to an understanding of the neurobiological basis of schizophrenia. She will also discuss how she has built on this foundation to reveal how the cortical circuits most afflicted in schizophrenia are regulated at the molecular level, and the potential for the development of therapies based on this work.
Arnsten joined Goldman-Rakic’s lab at Yale, in what was then the Department of Neurobiology, as a post-doctoral fellow. She built on Goldman-Rakic’s groundbreaking research on the prefrontal cortex, an area of the brain that serves as a mental sketchpad, supporting reasoning and top-down control of thoughts, actions and emotions.
Arnsten discovered that the neurotransmitter norepinephrine, acting on neurons via alpha-1 receptors, could dramatically disrupt the function of the prefrontal cortex, while its actions at alpha-2A receptors strengthened prefrontal connections. Eventually, this discovery led to the use of a drug that stimulates alpha-2A receptors, guanfacine, to treat cognitive disorders of the prefrontal cortex, particularly attention deficit and hyperactivity disorder
Arnsten’s research has gone on to explain the effects of stress on higher brain function at the molecular level. She has shown how that brain chemicals involved in arousal can rapidly alter the strength of prefrontal connections, a process called Dynamic Network Connectivity, lending them a remarkable level of flexibility. However, this process is also vulnerable and is affected by genetic changes associated with schizophrenia.
“It is remarkable that Amy is revealing actions at the molecular level in the brain’s highest order circuits, something that was a dream for Pat. I am sure that Pat would be so moved to know that so many people, including her colleagues at Yale, are building on her groundbreaking work,” said Pasko Rakic, who was married to Goldman-Rakic and worked closely with her for more than 20 years. Rakic is the former chairman of Yale’s Department of Neurobiology (now Neuroscience) and former director of the Kavli Institute.
It is remarkable that Amy is revealing actions at the molecular level in the brain’s highest order circuits, something that was a dream for Pat. I am sure that Pat would be so moved to know that so many people, including her colleagues at Yale, are building on her groundbreaking work.
Pasko Rakic
The Goldman-Rakic Prize was established in 2003 by Constance and Stephen Lieber after the death of Goldman-Rakic. It honors outstanding achievements in cognitive neuroscience that may lead to a greater understanding of underlying psychiatric or neurological disorders, and consists of $40,000 and an honorary lecture at Yale.
Among the previous recipients are inaugural winner Solomon Snyder of Johns Hopkins University and Marcus Raichle of Washington University, and more recently Michael Goldberg of Columbia University, Karl Deisseroth of Stanford University and Richard Huganir, also of Johns Hopkins.