Donald W. Pfaff, Ph.D.
Professor
Laboratory of Neurobiology and Behavior
E-mail: pfaff@rockefeller.edu
Dr. Pfaff uses neuroanatomical, neurochemical and neurophysiological methods to study the cellular mechanisms by which the
brain controls behavior. His laboratory’s research activities have 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 fi sh to primates. This
hormone-sensitive system apparently is a general
feature of the vertebrate brain, and Dr. Pfaff
recently found that knocking out the gene for
the estrogen receptor in animals prevents female
reproductive behavior. The deletion results both
in masculinizing female animals and, counterintuitively,
feminizing males’ behavior.
Second, Dr. Pfaff’s lab has worked out the
neural circuitry for hormone-dependent female
reproductive behavior, the fi rst behavior circuit
elucidated for any mammal. Third, they have
demonstrated that estrogens can turn on several
genes in the forebrain. Fourth, Dr. Pfaff has
shown that these gene products facilitate reproductive
behavior. Turning on the gene for the
progesterone receptor, for example, can stimulate
the hormone estrogen to turn on another
gene whose product is important for modulating
mating behavior. These four advances, taken
together, prove that specifi c chemicals acting in
specifi c parts of the brain can determine individual
behavioral responses.
In an experiment that lent support to the concept
of the “unity of the body,” Dr. Pfaff found
that the nervous system protein GnRH promotes
reproductive behavior and directs the pituitary
to stimulate the ovaries and testes. This action of
GnRH renders instinctive behaviors congruent
with the physiology of reproductive organs elsewhere
in the body. Dr. Pfaff’s lab subsequently
discovered that GnRH-producing neurons are
not actually born in the brain as other neurons are but are born in the olfactory epithelium and
then migrate up the nose and into the forebrain.
In humans, interruption of that migration, especially
in men, results in inadequate amounts of
the sex hormone testosterone.
Dr. Pfaff’s study of generalized arousal, responsible
for activating all behavioral responses,
led to the fi rst operational defi nition of the
term, enabling scientists to measure arousal
quantitatively in laboratory animals as well as
in human beings. In humans, defi cits in arousal
contribute to cognitive problems such as attention
defi cit hyperactivity disorder, autism and
Alzheimer’s disease. Analyzing the mechanisms
of arousal may lead to the development of
pharmacological methods to enhance alertness
during the day and sleep at night, as well as
the development of more precise anesthesiology.
Most 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 fi rst to register changes in food ability.
Finally, Dr. Pfaff has made fundamental
contributions to our understanding of how
the administration of sex hormones can affect
health. His lab recently showed that giving hormone
doses in pulses, rather than as a steady
exposure, may maximize the benefits and limit
the side effects now associated with hormone
therapies. In studies of rats, the scientists showed
that the actions of the hormone are crucial, at
both the level of the brain cell’s protective outer
membrane and inside the nucleus where the
cell’s DNA is housed, in triggering hormone dependent
gene expression and female mating
behavior. By limiting the estrogen exposure to
short pulses, the total dose can be kept smaller,
reducing negative effects.
CAREER
Dr. Pfaff 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.
He 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 recent book, Brain Arousal and Information
Theory. He is the recipient of a National Institutes
of Health Merit Award (2003 to 2013).
