Heads of Laboratories
Donald W. Pfaff, Ph.D.
Laboratory of Neurobiology and Behavior
Dr. Pfaff uses molecular, neuroanatomical and neurophysiological methods to study the cellular mechanisms by which the brain controls behavior. His laboratory’s research has focused on steroid hormone effects on nerve cells as they direct natural, instinctive behaviors, as well as the influences of hormones and genes on generalized brain arousal.
Dr. Pfaff’s research has proceeded through four steps to demonstrate how steroid hormone effects on nerve cells can direct natural, instinctive behaviors. First, Dr. Pfaff is known for discovering exact cellular targets for steroid hormones in the brain. A system of hypothalamic and limbic forebrain neurons with sex hormone receptors, discovered in rodents, was later found to be present in species ranging from fish to primates. Dr. Pfaff recently found that knocking out the gene for the estrogen receptor in animals prevents female reproductive behavior and maternal behaviors. Second, Dr. Pfaff’s lab has worked out the neural circuitry for hormone-dependent female reproductive behavior, the first behavior circuit elucidated for any mammal. Third, they have demonstrated that estrogens can turn on several genes in the forebrain. And fourth, Dr. Pfaff has shown that these gene products facilitate reproductive behavior. Together, these four advances proved how specific chemicals acting in specific parts of the brain determine individual behavioral responses.
In experiments uniting the immune, endocrine and nervous systems with behavior, Dr. Pfaff and his colleagues were the first to genetically link the neuroimmune system to emotional behavior, showing that mast cells in the brain mediate anxious behavior in mice. They also found that the nervous system protein GnRH promotes reproductive behavior as well as directs the pituitary to stimulate the ovaries and testes. Dr. Pfaff’s lab discovered that GnRH-producing neurons emerge from the olfactory epithelium and migrate up the nose and into the forebrain and that genetic interruption of that migration, especially in men, results in inadequate testosterone and loss of libido.
Dr. Pfaff’s study of generalized arousal, which activates all behavioral responses, led to the first operational definition of the term, enabling scientists to measure arousal quantitatively in laboratory animals and humans. In humans, deficits in arousal contribute to cognitive problems such as attention deficit/hyperactivity disorder, autism and Alzheimer’s disease, and analyzing the mechanisms of arousal may lead to pharmacological methods to enhance alertness and sleep, and to more precise anesthesiology. Recently, Dr. Pfaff and his colleagues pitted two forces of arousal — hunger and circadian rhythms — against each other, showing that these two pathways converge at the ventromedial hypothalamus and that this brain region is the first to register changes in food availability.
In conjunction with Alex Proekt, a visiting fellow in the lab, Dr. Pfaff and his team are using mathematical statistics to search for the quantitative properties of a brain emerging from a nonaroused state to an aroused state. Dr. Proekt demonstrated that the transition from inactivity to the activation of behavior follows a power law and then showed that emergence from anesthetic-caused unconsciousness is not a smooth, monotonic process but instead requires the brain to dwell temporarily in dynamic “hub states.” The team is interested in understanding the temporal patterns of neural activity in arousal systems that explain a person’s emergence from anesthesia.
Finally, studies in the lab have indicated that the origins of central nervous system arousal reside in the activities of large neurons, deep in the hindbrain, called nucleus gigantocellularis. A postdoc in the lab, Inna Tabansky, is using stem cell technology to produce these neurons from mouse embryonic stem cells. In parallel, her team is studying the normal lineage of nucleus gigantocellularis in the developing mouse brain. Taken together, her studies will address questions on the origins of arousal and have implications for certain neurodevelopmental disorders.
Dr. Pfaff graduated from Harvard College magna cum laude and received his Ph.D. from the Massachusetts Institute of Technology in 1965. He joined Rockefeller in 1966 as a postdoc and was named assistant professor in 1969. He was granted tenure in 1973 and promoted to full professor in 1978.
Dr. Pfaff is a member of the National Academy of Sciences and a fellow of the American Academy of Arts and Sciences. The author of several books on the brain and behavior, he received the 2005 Award for Excellence in Professional and Scholarly Publishing (medical science category) of the Association of American Publishers for his book, Brain Arousal and Information Theory. He received the 2010 Ipsen Foundation Prize in Neuronal Plasticity and the Daniel S. Lehrman Lifetime Achievement Award in Behavioral Neuroendocrinology in 2011.
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