Elizabeth Gould (psychologist)

Last updated
Elizabeth Gould
Born1962 (age 61–62)
New York
Alma mater UCLA
Scientific career
Fields Neuroscience
Institutions Princeton University

Elizabeth Gould (born 1962) [1] is an American neuroscientist and the Dorman T. Warren Professor of Psychology at Princeton University. [2] [3] She was an early investigator of adult neurogenesis in the hippocampus, a research area that continues to be controversial. [4] [5] [6] In November 2002, Discover magazine listed her as one of the 50 most important women scientists. [7]

Contents

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. Specifically, she and Dr. Heather A. Cameron reported on adrenal steroid control of adult neurogenesis in rat dentate gyrus. [8] Additionally, her work has provided evidence of neurogenesis in the adult primate neocortex. [9] Gould and the researchers reported new neurons in adult marmoset 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. [4]

Education and early research

Gould was born in 1962 [1] and received her Ph.D. in behavioral neuroscience in 1988 at UCLA. In 1989, she joined the lab of Bruce McEwen at Rockefeller University as a postdoctoral researcher [10] investigating the effect of stress hormones on rat brains. Gould's research focused on the death of cells in the hippocampus. While Gould was documenting the degeneration of these brains, she discovered evidence that pointed to the idea that the brain might also heal itself. [11]

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 an explanation as to what she was doing wrong. She ended up looking through numerous papers in the Rockefeller stacks. 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 in favor of Pasko Rakic's findings. [12]

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. [13] [1] However, other scientists continued to support Rakic's doctrine which denied the possibility of neurogenesis in mammals. 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.” [14] Like Altman before him, Kaplan abandoned his work in neurogenesis. [14]

Confronting Rakic's data

Gould spent the next eight years quantifying endless numbers of radioactive rat hippocampi in pursuit of neurogenesis. Gould became a member of the Princeton faculty in 1997. The very next year, in a series of papers, Gould began documenting neurogenesis in primates, directly confronting Rakic's data. She demonstrated that adult marmosets created new neurons in their brains, especially in the olfactory cortex and the hippocampus. [14] By 1999, Rakic admitted that neurogenesis was real. [14] To that end he published a paper in the Proceedings of the National Academy of Sciences that reported seeing new neurons in the hippocampus of macaques. [15]

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). [16]

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. [16]

Research by Gould and her colleagues

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. [17]

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. [18] [19] 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. [20]

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. [21] [22]

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. [23] 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. [4]

Honors and awards

Gould received a multitude of awards throughout the duration of her career. From 1989 to 1991, Gould was awarded an NRSA Individual postdoctoral fellowship. [24] From 1991 to 1992, she was awarded the Winston Tri-Institutional (Rockefeller, Cornell, Sloan-Kettering) fellowship. From 1992 to 1993, she was awarded an American Paralysis Association grant. [25] From 1993 to 1994, she was awarded the NIMH RO3 small grant. From 1994 to 1996, she was awarded the NARSAD Young Investigator Award. [11] From 1994 to 1999, she was awarded the NIMH FIRST award. In 2000, she was awarded the National Academy of Sciences Troland Award. [26] In 2006, she was awarded the NARSAD Distinguished Investigator Award. [11] 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. [27]

Related Research Articles

<span class="mw-page-title-main">Hippocampus</span> Vertebrate brain region involved in memory consolidation

The hippocampus is a major component of the brain of humans and other vertebrates. Humans and other mammals have two hippocampi, one in each side of the brain. The hippocampus is part of the limbic system, and plays important roles in the consolidation of information from short-term memory to long-term memory, and in spatial memory that enables navigation. The hippocampus is located in the allocortex, with neural projections into the neocortex, in humans as well as other primates. The hippocampus, as the medial pallium, is a structure found in all vertebrates. In humans, it contains two main interlocking parts: the hippocampus proper, and the dentate gyrus.

<span class="mw-page-title-main">Limbic system</span> Set of brain structures involved in emotion and motivation

The limbic system, also known as the paleomammalian cortex, is a set of brain structures located on both sides of the thalamus, immediately beneath the medial temporal lobe of the cerebrum primarily in the forebrain.

<span class="mw-page-title-main">Androgen</span> Any steroid hormone that promotes male characteristics

An androgen is any natural or synthetic steroid hormone that regulates the development and maintenance of male characteristics in vertebrates by binding to androgen receptors. This includes the embryological development of the primary male sex organs, and the development of male secondary sex characteristics at puberty. Androgens are synthesized in the testes, the ovaries, and the adrenal glands.

<span class="mw-page-title-main">Dentate gyrus</span> Region of the hippocampus in the brain

The dentate gyrus (DG) is part of the hippocampal formation in the temporal lobe of the brain, which also includes the hippocampus and the subiculum. The dentate gyrus is part of the hippocampal trisynaptic circuit and is thought to contribute to the formation of new episodic memories, the spontaneous exploration of novel environments and other functions.

<span class="mw-page-title-main">Adult neurogenesis</span> Generating of neurons from neural stem cells in adults

Adult neurogenesis is the process in which neurons are generated from neural stem cells in the adult. This process differs from prenatal neurogenesis.

Neural stem cells (NSCs) are self-renewing, multipotent cells that firstly generate the radial glial progenitor cells that generate the neurons and glia of the nervous system of all animals during embryonic development. Some neural progenitor stem cells persist in highly restricted regions in the adult vertebrate brain and continue to produce neurons throughout life. Differences in the size of the central nervous system are among the most important distinctions between the species and thus mutations in the genes that regulate the size of the neural stem cell compartment are among the most important drivers of vertebrate evolution.

Joseph Altman was an American biologist who worked in the field of neurobiology.

<span class="mw-page-title-main">Subgranular zone</span>

The subgranular zone (SGZ) is a brain region in the hippocampus where adult neurogenesis occurs. The other major site of adult neurogenesis is the subventricular zone (SVZ) in the brain.

Radiation-induced cognitive decline describes the possible correlation between radiation therapy and cognitive impairment. Radiation therapy is used mainly in the treatment of cancer. Radiation therapy can be used to cure care or shrink tumors that are interfering with quality of life. Sometimes radiation therapy is used alone; other times it is used in conjunction with chemotherapy and surgery. For people with brain tumors, radiation can be an effective treatment because chemotherapy is often less effective due to the blood–brain barrier. Unfortunately for some patients, as time passes, people who received radiation therapy may begin experiencing deficits in their learning, memory, and spatial information processing abilities. The learning, memory, and spatial information processing abilities are dependent on proper hippocampus functionality. Therefore, any hippocampus dysfunction will result in deficits in learning, memory, and spatial information processing ability.

The trisynaptic circuit or trisynaptic loop is a relay of synaptic transmission in the hippocampus. The circuit was initially described by the neuroanatomist Santiago Ramon y Cajal, in the early twentieth century, using the Golgi staining method. After the discovery of the trisynaptic circuit, a series of research has been conducted to determine the mechanisms driving this circuit. Today, research is focused on how this loop interacts with other parts of the brain, and how it influences human physiology and behaviour. For example, it has been shown that disruptions within the trisynaptic circuit lead to behavioural changes in rodent and feline models.

<span class="mw-page-title-main">Hippocampus anatomy</span>

Hippocampus anatomy describes the physical aspects and properties of the hippocampus, a neural structure in the medial temporal lobe of the brain. It has a distinctive, curved shape that has been likened to the sea-horse monster of Greek mythology and the ram's horns of Amun in Egyptian mythology. This general layout holds across the full range of mammalian species, from hedgehog to human, although the details vary. For example, in the rat, the two hippocampi look similar to a pair of bananas, joined at the stems. In primate brains, including humans, the portion of the hippocampus near the base of the temporal lobe is much broader than the part at the top. Due to the three-dimensional curvature of this structure, two-dimensional sections such as shown are commonly seen. Neuroimaging pictures can show a number of different shapes, depending on the angle and location of the cut.

<span class="mw-page-title-main">Granule cell</span> Type of neuron with a very small cell body

The name granule cell has been used for a number of different types of neurons whose only common feature is that they all have very small cell bodies. Granule cells are found within the granular layer of the cerebellum, the dentate gyrus of the hippocampus, the superficial layer of the dorsal cochlear nucleus, the olfactory bulb, and the cerebral cortex.

Endogenous regeneration in the brain is the ability of cells to engage in the repair and regeneration process. While the brain has a limited capacity for regeneration, endogenous neural stem cells, as well as numerous pro-regenerative molecules, can participate in replacing and repairing damaged or diseased neurons and glial cells. Another benefit that can be achieved by using endogenous regeneration could be avoiding an immune response from the host.

<span class="mw-page-title-main">Glucocorticoids in hippocampal development</span> HippoCampus

The hippocampus is an area of the brain integral to learning and memory. Removal of this structure can result in the inability to form new memories as most famously demonstrated in a patient referred to as HM. The unique morphology of the hippocampus can be appreciated without the use of special stains and this distinct circuitry has helped further the understanding of neuronal signal potentiation. The following will provide an introduction to hippocampal development with particular focus on the role of glucocorticoid signaling.

Neurogenesis is the process by which nervous system cells, the neurons, are produced by neural stem cells (NSCs). In short, it is brain growth in relation to its organization. This occurs in all species of animals except the porifera (sponges) and placozoans. Types of NSCs include neuroepithelial cells (NECs), radial glial cells (RGCs), basal progenitors (BPs), intermediate neuronal precursors (INPs), subventricular zone astrocytes, and subgranular zone radial astrocytes, among others.

Attila Losonczy is a Hungarian neuroscientist, Professor of Neuroscience at Columbia University Medical Center. Losonczy's main area of research is on the relationship between neural networks and behavior, specifically with regard to learning in the hippocampus.

Christine Denny is an American neuroscientist and associate professor of Clinical Neurobiology in Psychiatry in the Department of Psychiatry at Columbia University Irving Medical Center in New York City. Denny investigates the molecular mechanisms underlying learning and memory. She developed a novel technique to label neurons that encode specific memories. She used this technique to probe what happens to hippocampal memory traces in different disease states.

Adult neurogenesis is the process in which new neurons are born and subsequently integrate into functional brain circuits after birth and into adulthood. Avian species including songbirds are among vertebrate species that demonstrate particularly robust adult neurogenesis throughout their telencephalon, in contrast with the more limited neurogenic potential that are observed in adult mammals after birth. Adult neurogenesis in songbirds is observed in brain circuits that underlie complex specialized behavior, including the song control system and the hippocampus. The degree of postnatal and adult neurogenesis in songbirds varies between species, shows sexual dimorphism, fluctuates seasonally, and depends on hormone levels, cell death rates, and social environment. The increased extent of adult neurogenesis in birds compared to other vertebrates, especially in circuits that underlie complex specialized behavior, makes birds an excellent animal model to study this process and its functionality. Methods used in research to track adult neurogenesis in birds include the use of thymidine analogues and identifying endogenous markers of neurogenesis. Historically, the discovery of adult neurogenesis in songbirds substantially contributed to establishing the presence of adult neurogenesis and to progressing a line of research tightly associated with many potential clinical applications.

<span class="mw-page-title-main">Neurogenesis hypothesis of depression</span> Theory of depression

Adult neurogenesis is the process by which functional, mature neurons are produced from neural stem cells (NSCs) in the adult brain. In most mammals, including humans, it only occurs in the subgranular zone of the hippocampus, and in the olfactory bulb. The neurogenesis hypothesis of depression proposes that major depressive disorder is caused, at least partly, by impaired neurogenesis in the subgranular zone of the hippocampus.

<span class="mw-page-title-main">Heather Cameron (neuroscientist)</span> American neuroscientist

Heather A. Cameron is an American neuroscientist who researches adult neurogenesis and diseases involving the hippocampus. She is the chief of the neuroplasticity section at the National Institute of Mental Health.

References

  1. 1 2 3 Specter, Michael (July 23, 2001). "Rethinking the Brain How the songs of canaries upset a fundamental principle of science". Michael Specter. The New Yorker. Retrieved 28 September 2018.
  2. ↑ "Elizabeth Gould, Ph.D." Brain and Behavior. 2017-04-03. Retrieved 28 September 2018.
  3. ↑ "Elizabeth Gould". Princeton Neuroscience Institute. Retrieved 28 September 2018.
  4. 1 2 3 Epp, Jonathan R.; Chow, Carmen; Galea, Liisa A. M. (16 April 2013). "Hippocampus-dependent learning influences hippocampal neurogenesis". Frontiers in Neuroscience. 7: 57. doi: 10.3389/FNINS.2013.00057 . ISSN   1662-453X. PMC   3627134 . PMID   23596385. Wikidata   Q36768019.
  5. ↑ Kempermann, Gerd; Gage, Fred H.; Aigner, Ludwig; et al. (19 April 2018). "Human Adult Neurogenesis: Evidence and Remaining Questions". Cell Stem Cell . 23 (1): 25–30. doi:10.1016/J.STEM.2018.04.004. ISSN   1934-5909. PMC   6035081 . PMID   29681514. Wikidata   Q52804530.
  6. ↑ Andreae, Laura C. (11 April 2018). "Adult neurogenesis in humans: Dogma overturned, again and again?". Science Translational Medicine . 10 (436): eaat3893. doi:10.1126/SCITRANSLMED.AAT3893. ISSN   1946-6234. Wikidata   Q64385753.
  7. ↑ Svitil, Kathy (1 November 2002). "The 50 Most Important Women in Science". Discover. Retrieved 21 December 2014.
  8. ↑ Cameron, H.A.; Gould, E. (July 1994). "Adult neurogenesis is regulated by adrenal steroids in the dentate gyrus". Neuroscience. 61 (2): 203–209. doi:10.1016/0306-4522(94)90224-0. PMID   7969902. S2CID   16297590.
  9. ↑ Gould, Elizabeth; Reeves, Alison J.; Graziano, Michael S. A.; Gross, Charles G. (October 1999). "Neurogenesis in the Neocortex of Adult Primates". Science. 286 (5439): 548–552. doi:10.1126/science.286.5439.548. PMID   10521353. S2CID   14687148.
  10. ↑ Woolley, Catherine S. (2007). "Estrogen and synapses in the hippocampus". In Bear, Mark F.; Connors, Barry W.; Paradiso, Michael A. (eds.). Neuroscience : exploring the brain (Fourth ed.). Baltimore, MD: Lippincott Williams & Wilkins. p. 558. ISBN   978-1451109542.{{cite book}}: |journal= ignored (help)
  11. 1 2 3 "NARSAD Grantees at the Leading Edge: A Quarter-Century of Groundbreaking Discoveries about the Brain's Plasticity". Brain and Behavior. October 22, 2013. Retrieved 28 September 2018.
  12. ↑ Rakic, P (1 February 1974). "Neurons in rhesus monkey visual cortex: systematic relation between time of origin and eventual disposition". Science. 183 (4123): 425–7. Bibcode:1974Sci...183..425R. doi:10.1126/science.183.4123.425. PMID   4203022. S2CID   10881759.
  13. ↑ Snyder, Jason (March 7, 2018). "WTF! No neurogenesis in humans??". The Snyder Lab. Retrieved 28 September 2018.
  14. 1 2 3 4 Lehrer, Jonah (2006). "The reinvention of self" (PDF). SEED. No. February/March. p. 63. Retrieved 28 September 2018.
  15. ↑ Kornack, DR; Rakic, P (11 May 1999). "Continuation of neurogenesis in the hippocampus of the adult macaque monkey". Proceedings of the National Academy of Sciences of the United States of America. 96 (10): 5768–73. Bibcode:1999PNAS...96.5768K. doi: 10.1073/pnas.96.10.5768 . PMC   21935 . PMID   10318959.
  16. 1 2 "Elizabeth Gould". Princeton University. Retrieved 31 July 2017.
  17. ↑ Tanapat, Patima; Hastings, Nicholas B.; Gould, Elizabeth (17 January 2005). "Ovarian steroids influence cell proliferation in the dentate gyrus of the adult female rat in a dose- and time-dependent manner". The Journal of Comparative Neurology. 481 (3): 252–265. doi:10.1002/cne.20385. PMID   15593136. S2CID   16185380.
  18. ↑ Leuner, B.; Kozorovitskiy, Y.; Gross, C. G.; Gould, E. (16 October 2007). "Diminished adult neurogenesis in the marmoset brain precedes old age". Proceedings of the National Academy of Sciences. 104 (43): 17169–17173. Bibcode:2007PNAS..10417169L. doi: 10.1073/pnas.0708228104 . PMC   2040400 . PMID   17940008.
  19. ↑ Gould, E; McEwen, BS; Tanapat, P; Galea, LA; Fuchs, E (1 April 1997). "Neurogenesis in the dentate gyrus of the adult tree shrew is regulated by psychosocial stress and NMDA receptor activation". The Journal of Neuroscience . 17 (7): 2492–2498. doi:10.1523/JNEUROSCI.17-07-02492.1997. ISSN   0270-6474. PMC   6573503 . PMID   9065509. Wikidata   Q64385755.
  20. ↑ Opendak, Maya; Gould, Elizabeth (March 2015). "Adult neurogenesis: a substrate for experience-dependent change". Trends in Cognitive Sciences. 19 (3): 151–161. doi:10.1016/j.tics.2015.01.001. PMID   25715908. S2CID   16384656.
  21. ↑ Lieberwirth, Claudia; Wang, Zuoxin (2012). "The Social Environment and Neurogenesis in the Adult Mammalian Brain". Frontiers in Human Neuroscience. 6: 118. doi: 10.3389/fnhum.2012.00118 . PMC   3347626 . PMID   22586385.
  22. ↑ Leuner, Benedetta; Gould, Elizabeth (January 2010). "Structural Plasticity and Hippocampal Function". Annual Review of Psychology. 61 (1): 111–140. doi:10.1146/annurev.psych.093008.100359. PMC   3012424 . PMID   19575621.
  23. ↑ LaDage, Lara D. (September 2015). "Environmental Change, the Stress Response, and Neurogenesis: Fig. 1". Integrative and Comparative Biology. 55 (3): 372–383. doi: 10.1093/icb/icv040 . PMID   25980567.
  24. ↑ Gould, Elizabeth; Allan, Mark D.; McEwen, Bruce S. (August 1990). "Dendritic spine density of adult hippocampal pyramidal cells is sensitive to thyroid hormone". Brain Research. 525 (2): 327–329. doi:10.1016/0006-8993(90)90884-E. PMID   2253032. S2CID   14935477.
  25. ↑ GOULD, ELIZABETH (November 1994). "The Effects of Adrenal Steroids and Excitatory Input on Neuronal Birth and Survival". Annals of the New York Academy of Sciences. 743 (1 Hormonal Rest): 73–92. Bibcode:1994NYASA.743...73G. doi:10.1111/j.1749-6632.1994.tb55788.x. PMID   7802420. S2CID   1585142.
  26. ↑ "Troland Research Awards". National Academy of Science. Retrieved 27 September 2018.
  27. ↑ "Spring 2009 News in Brief". RSA. Archived from the original on 5 January 2011. Retrieved 28 December 2010.
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