Elizabeth Gould (psychologist)

Elizabeth Gould was one of the first to find evidence of adult neurogenesis in the hippocampus. Her research, in reviving the idea of neurogenesis, was instrumental in setting off a frenzy of research resulting in neurogenesis being currently one of the hottest topics in neuroscience.

Gould is professor of psychology at Princeton University's Department of Psychology.

Gould discovered evidence of adult neurogenesis in the hippocampus and olfactory bulb of rats, marmosets and macaque monkeys. In her early studies, she laid the groundwork for understanding the relationship between stress and adult neurogenesis.

Her work has shown some evidence of neurogenesis in the adult neocortex. A study by Dr. Gould, [1] et al., was published in the October 15, 1999 issue of Science, investigating neurogenesis in the adult primate neocortex. Gould and the researchers reported new neurons in adult macaque monkeys are added to three neocortical association areas important in cognitive function: the prefrontal, inferior temporal and posterior parietal cortex. The new neurons appeared to originate in the subventricular zone, where stem cells giving rise to other cell types are located. They then migrate through the white matter to the neocortex, extending axons. Continual addition of neurons in adulthood apparently contributes to association neocortex functions.

As these monkeys are close genetically to humans it is probably not unthinkable to suggest the process of forming new neurons in the cortex may go on in all adult animals with brains, including humans. This possibility makes Gould's work of even greater significance.

Education and path to discovery

Gould received her Ph.D. in behavioral neuroscience in 1988 at UCLA. In 1989, she was a young post-doc working in the lab of Bruce McEwen at Rockefeller University, investigating the effect of stress hormones on rat brains. Chronic stress is devastating to neurons, and Gould’s research focused on the death of cells in the hippocampus. (Pasko Rakic's declaration that there was no such thing as neurogenesis was entrenched dogma at that time.) The research was exciting because stress research was a booming field at that time also. However, it was extremely hard work necessitating killing her rats at various time points, pluck their tiny brains out of their cranial encasing, cut through their cortex, slice the hippocampus thinner than a sheet of paper, and with great care count the dying neurons under a microscope. While Gould was documenting the degeneration of these brains, she happened upon something seemingly inexplicable. Evidence pointed to the idea that the brain might also heal itself. She explains, “At first, I assumed I must be counting [the neurons] incorrectly,” Gould said. “There were just too many cells.”

Uncovering earlier work in neurogenesis

Confused by this anomaly, Gould assumed she must have been making some simple experimental error, and she went to the Rockefeller library, hoping she could find explanation as to what she was doing wrong. (This all took place before the Internet.) She ended up looking through numerous dusty papers in the Rockefeller stacks. In one such science journal, buried there for 27 years, Gould found the explanation she needed, though not the one she was expecting. Several 1962 papers revealed the research at MIT by Joseph Altman claiming that adult rats, cats, and guinea pigs all formed new neurons. Altman’s results had been at first ridiculed, then ignored, and quickly forgotten. As a result, the field of neurogenesis had died before it could get started.

Further investigation by Gould revealed that a decade later Michael Kaplan, at the University of New Mexico, had used an electron microscope to image neurons giving birth. Kaplan had, he believed, discovered new neurons everywhere in the mammalian brain, including the cortex. Yet even with this visual evidence, science clung to Rakic's doctrine which denied the possibility of neurogenesis. Kaplan is reported as remembering Rakic telling him that “Those [cells] may look like neurons in New Mexico, but they don’t in New Haven.” Faced with the toxicity of this type of criticism, like Altman before him, Kaplan had abandoned his work in neurogenesis.

Confronting Rakic's data

Gould was more than intrigued. She would spend the next eight years quantifying endless numbers of radioactive rat hippocampii in pursuit of neurogenesis. Eventually the painstaking manual labor bore fruit as Gould’s data caused a shift in the neuroscience paradigm and neurogenesis had finally become a real science. After having been worn down by the continually criticism of her data during her post-doc, Gould was eventually offered a job at Princeton. The very next year, in a series of landmark papers, Gould began documenting neurogenesis in primates, thus confronting Rakic’s data directly. She demonstrated that adult marmosets created new neurons in their brains, especially in the olfactory cortex and the hippocampus. By 1999, even Rakic finally had to admit that neurogenesis was real. To that end he published a paper in the [2] Proceedings of the National Academy of Sciences that reported seeing new neurons in the hippocampus of macaques.

Current work

Gould's laboratory at Princeton studies the production of new neurons in the early postnatal and adult mammalian brain. Her laboratory explores issues related to the regulation of cell production and survival in three brain regions the hippocampus, the olfactory bulb and the neocortex in rodents and primates (marmosets and macaques).

Gould and her colleagues believe the answer to the question, ‘What possible function could late-generated cells serve?’ could have immense significance in neuroscience and their investigations are guided mostly by this question. Gould and her team are also endeavoring to discover how hormones modulate the production of new neurons and how experience affects new cell production and if so, through what underlying mechanisms.

Representative studies of Gould and her colleagues' research

Hormonal regulation of cell production
Gould and her colleagues found that the ovarian steroid estrogen enhances cell proliferation in the dentate gyrus of the adult rat. This effect can be seen following ovariectomy and hormone replacement as well as under naturally occurring changes in hormone levels. They discovered that cell proliferation peaks during proestrus, a time when estrogen levels are highest. Also and conversely, steroid hormones of the adrenal glands were found to inhibit cell proliferation in the dentate gyrus but do so indirectly via an NMDA receptor-dependent mechanism.

Experience-dependent changes in neurogenesis
Gould’s research has shown that exposure of aversive stimuli results in a decrease in cell proliferation in the dentate gyrus of adult rats, tree shrews and marmoset monkeys. Gould and her colleagues have shown that social stress inhibits cell production in these three species in a series of studies. Furthermore, they have discovered that exposure of adult rats to the odors of natural predators, but not other novel odors, suppresses the proliferation of cells in the dentate gyrus. This effect was found to be dependent on adrenal steroids because the prevention of the stress-induced rise in glucocorticoids (by adrenalectomy and replacement with low-dose corticosterone in the drinking water) eliminated the inhibitory effect of fox odor on cell production.

The importance of complex environments
Gould’s team has observed that many new cells in the hippocampus of adult rats and monkeys do not survive in animals living under standard laboratory conditions. In rodents, they discovered that these cells can be rescued by exposing the animals to more complex environments. These results they believe reflect the deprived laboratory conditions in which experimental animals live. This they also suspect is a phenomenon, that is probably, even more pronounced in primates with higher social needs than in rodents. The Gould team is continuing to explore this issue by examining the brains of adult rats living in a visible burrow system and adult monkeys living in semi-naturalistic conditions with opportunities for foraging and other natural activities.

The functional role of new neurons
Although the function of new neurons in the adult brain is as yet unknown Gould and her colleagues have begun to conjecture possibilities. So many new neurons are generated in the hippocampus and these cells appear to be a sensitive to experience, therefore it seems likely to the Gould team that they participate in hippocampal function. They are exploring the possibility that new neurons participate in two functions of the hippocampus, learning and modulation of the stress response. They have shown that learning enhances the number of new neurons but only under certain conditions. Furthermore they have discovered, experimental depletion of new neurons is associated with impairment in certain types of learning but not others. A decrease in the number of new neurons following treatment with anti-mitotic drugs impairs trace eye blink conditioning but not spatial learning in a Morris water maze, both hippocampal-dependent tasks.

Teaching and leadership style

Dr. Gould insists on being called Liz. She doesn’t talk about her research in the abstract manner of many scientists, but rather guides one through the experimental process, confessing the difficulties and ambiguities she and her colleagues have encountered along the way. Gould has a casual air about her that conceals real tenacity. It is said that four days after giving birth to her third child, Gould was back at work, lecturing to undergraduates. She has always worked long hours, and expects nothing less of her team. Through all the excitement around neurogenesis, Gould herself has managed to remain at the cutting edge of the field.

Gould reflects

When Gould first presented her work at the Society of Neuroscience’s annual meeting, there was no such thing as the field of neurogenesis whose birth she was there to announce; her work was filed away in the “spinal cord rejuvenation” section. Today, the scientist is almost frightened at the way her field has grown so large so quickly: “I do get worried sometimes that neurogenesis has gotten overblown. The science of it still isn’t clear. But at the same time I understand why there is so much enthusiasm for the idea. It’s a new way of looking at a lot of old problems.”

Honors and Awards

In 2009 she was awarded the Benjamin Franklin medal by the Royal Society for the encouragement of Arts, Manufactures and Commerce (RSA) for her groundbreaking work on neurogenesis.

External links

• Gould's Princeton webpage
• TRENDS in Neurosciences, 10 October 2001, Michael S. Kaplan MD, PhD
• Article about Gould
• Science 15 October 1999:Vol. 286. no. 5439, pp. 548 - 52 "Neurogenesis in the Neocortex of Adult Primates," Elizabeth Gould, Alison J. Reeves, Michael S. A. Graziano, Charles G. Gross
• RSA Vision webcast - Elizabeth Gould on how "Experience Influences the Brain"
• Society of Neuroscience official website
• National Academy of Sciences official website