Stress and Memory Formation Across the Female Lifespan

Summary

Principal Investigator: Tracey Shors
Abstract: DESCRIPTION (provided by applicant): It has become increasingly clear that males and females differ even more dramatically than we previously thought. Not only do they exhibit differing responses to stress and environmental experience, but they can also respond in opposite directions. In rats, exposure to an acute stressful event enhances associative learning in males while dramatically impairing performance in females (Wood et al 2001, Wood &Shors 1998;Shors et al., 1998, 2002). These opposite effects of stress on memory formation are accompanied by similarly opposite effects on the presence of dendritic spines in the hippocampal formation (Shors et al 2001). Moreover, these opposite effects of stress are mediated by different hormonal systems between the sexes (Wood et al 2001, Beylin &Shors 2002). Sex differences usually arise from activational and organizational effects of sex hormones which fluctuate across the lifespan, especially in females. The experiments described in this competing continuation capitalize on hormonal fluctuations and changes in emotionality that occur during very early development, puberty, post-partum and menopause. They are designed to associate and dissociate changes in learning ability and responses to stressful experience with changes in hormones and density of dendritic spines in the hippocampal formation. Finally, experiments are designed to explore a potential relationship between sex differences in learning and the expression of growth hormone (GH) in the hippocampus, a gene that is preferentially induced by learning (Donahue et al., 2002). Techniques include trace eyeblink conditioning in the rat, Golgi impregnation and light microscope analysis, real-time polymerase chain reaction, in situ hybridization, radioimmunoassay, and surgical manipulation of glucocorticoids and ovarian hormones. Overall, these studies will identity the neuronal and hormonal mechanisms that underlie sex differences in learning and opposite responses to stressful experience in males versus females. Because mental disorders often emerge or are exacerbated during these life changes, the studies will provide insight into sex differences in mental illness, especially those experienced so frequently by women: post-traumatic stress disorder (PTSD), unipolar, post-partum and post-menopausal depression, as well as Alzheimer's disease.
Funding Period: 2009-09-30 - 2010-09-29
more information: NIH RePORT

Top Publications

  1. pmc Physical skill training increases the number of surviving new cells in the adult hippocampus
    Daniel M Curlik
    Department of Psychology and Center for Collaborative Neuroscience, Rutgers University, Piscataway, New Jersey, USA
    PLoS ONE 8:e55850. 2013
  2. pmc Developmental mercury exposure elicits acute hippocampal cell death, reductions in neurogenesis, and severe learning deficits during puberty
    Anthony Falluel-Morel
    Department of Neuroscience and Cell Biology, UMDNJ Robert Wood Johnson Medical School, Piscataway, New Jersey, USA
    J Neurochem 103:1968-81. 2007
  3. pmc The hippocampus is necessary for enhancements and impairments of learning following stress
    Debra A Bangasser
    Department of Psychology and Center for Collaborative Neuroscience, Rutgers University, 152 Frelinghuysen Road, Piscataway, New Jersey 08854, USA
    Nat Neurosci 10:1401-3. 2007
  4. pmc The neuropeptide VGF produces antidepressant-like behavioral effects and enhances proliferation in the hippocampus
    Smita Thakker-Varia
    Department of Neuroscience and Cell Biology, University of Medicine and Dentistry of New Jersey, Robert Wood Johnson Medical School, Piscataway, New Jersey 08854 5635, USA
    J Neurosci 27:12156-67. 2007
  5. pmc Neurogenesis, learning and associative strength
    Jaylyn Waddell
    Department of Psychology and Center for Collaborative Neuroscience, Rutgers University, Piscataway, NJ 08854, USA
    Eur J Neurosci 27:3020-8. 2008
  6. pmc Stressful experience has opposite effects on dendritic spines in the hippocampus of cycling versus masculinized females
    Christina Dalla
    Department of Psychology and Center for Collaborative Neuroscience, Rutgers University, 152 Frelinghuysen Road, Piscataway, NJ 08854, USA
    Neurosci Lett 449:52-6. 2009
  7. pmc The prefrontal cortex communicates with the amygdala to impair learning after acute stress in females but not in males
    Lisa Y Maeng
    Department of Psychology and Center for Collaborative Neuroscience, Rutgers University, Piscataway, New Jersey 08854, USA
    J Neurosci 30:16188-96. 2010
  8. pmc Chemotherapy disrupts learning, neurogenesis and theta activity in the adult brain
    Miriam S Nokia
    Department of Psychology, University of Jyvaskyla, PO Box 35, 40014 Jyvaskyla, Finland
    Eur J Neurosci 36:3521-30. 2012
  9. pmc Neurogenesis and the spacing effect: learning over time enhances memory and the survival of new neurons
    Helene M Sisti
    Department of Psychology and Center for Collaborative Neuroscience, Rutgers University, Piscataway, New Jersey, USA
    Learn Mem 14:368-75. 2007
  10. pmc Learning during motherhood: A resistance to stress
    Benedetta Leuner
    Department of Psychology and Center for Collaborative Neuroscience, Rutgers University, 152 Frelinghuysen Road, Piscataway, NJ 08854, USA
    Horm Behav 50:38-51. 2006

Scientific Experts

  • Tracey J Shors
  • D A Bangasser
  • G E Hodes
  • Miriam S Nokia
  • Jaylyn Waddell
  • Deepak P Srivastava
  • Christina Dalla
  • Daniel M Curlik
  • Lisa Y Maeng
  • Benedetta Leuner
  • Helene M Sisti
  • Abigail S Whetstone
  • Megan L Anderson
  • Carol Edgecomb
  • Anthony Falluel-Morel
  • Smita Thakker-Varia
  • Elizabeth Gould
  • Christine P Donahue
  • Prateek R Agarwal
  • Efstathios B Papachristos
  • Katie Sokolowski
  • Jacob Nettleton
  • Arnold L Glass
  • Ira B Black
  • Parizad M Bilimoria
  • Xiaofeng Zhou
  • Janet Alder
  • Emanuel DiCicco-Bloom
  • Jennifer Jernstedt Krol
  • Kenneth S Kosik

Detail Information

Publications37

  1. pmc Physical skill training increases the number of surviving new cells in the adult hippocampus
    Daniel M Curlik
    Department of Psychology and Center for Collaborative Neuroscience, Rutgers University, Piscataway, New Jersey, USA
    PLoS ONE 8:e55850. 2013
    ..Therefore, physical skill training that does not depend on the hippocampus can effectively increase the number of surviving cells in the adult hippocampus, the vast majority of which become mature neurons...
  2. pmc Developmental mercury exposure elicits acute hippocampal cell death, reductions in neurogenesis, and severe learning deficits during puberty
    Anthony Falluel-Morel
    Department of Neuroscience and Cell Biology, UMDNJ Robert Wood Johnson Medical School, Piscataway, New Jersey, USA
    J Neurochem 103:1968-81. 2007
    ..In aggregate, these studies indicate that exposure to one dose of MeHg during the perinatal period acutely induces apoptotic cell death, which results in later deficits in hippocampal structure and function...
  3. pmc The hippocampus is necessary for enhancements and impairments of learning following stress
    Debra A Bangasser
    Department of Psychology and Center for Collaborative Neuroscience, Rutgers University, 152 Frelinghuysen Road, Piscataway, New Jersey 08854, USA
    Nat Neurosci 10:1401-3. 2007
    ..Thus, the hippocampus is necessary for modifying learning in males and females after acute stressful experience...
  4. pmc The neuropeptide VGF produces antidepressant-like behavioral effects and enhances proliferation in the hippocampus
    Smita Thakker-Varia
    Department of Neuroscience and Cell Biology, University of Medicine and Dentistry of New Jersey, Robert Wood Johnson Medical School, Piscataway, New Jersey 08854 5635, USA
    J Neurosci 27:12156-67. 2007
    ..Thus, VGF may act downstream of BDNF and exert its effects as an antidepressant-like agent by enhancing neurogenesis in the hippocampus...
  5. pmc Neurogenesis, learning and associative strength
    Jaylyn Waddell
    Department of Psychology and Center for Collaborative Neuroscience, Rutgers University, Piscataway, NJ 08854, USA
    Eur J Neurosci 27:3020-8. 2008
    ..Thus, learning can rescue the majority of cells expressed at the beginning of training, and does so most effectively when acquisition requires many trials...
  6. pmc Stressful experience has opposite effects on dendritic spines in the hippocampus of cycling versus masculinized females
    Christina Dalla
    Department of Psychology and Center for Collaborative Neuroscience, Rutgers University, 152 Frelinghuysen Road, Piscataway, NJ 08854, USA
    Neurosci Lett 449:52-6. 2009
    ..Such a process may represent a mechanism for altering learning abilities after an acute traumatic experience...
  7. pmc The prefrontal cortex communicates with the amygdala to impair learning after acute stress in females but not in males
    Lisa Y Maeng
    Department of Psychology and Center for Collaborative Neuroscience, Rutgers University, Piscataway, New Jersey 08854, USA
    J Neurosci 30:16188-96. 2010
    ..Together, these data indicate that the mPFC is critically involved in females during stress to impair subsequent learning and does so via communication with the amygdala...
  8. pmc Chemotherapy disrupts learning, neurogenesis and theta activity in the adult brain
    Miriam S Nokia
    Department of Psychology, University of Jyvaskyla, PO Box 35, 40014 Jyvaskyla, Finland
    Eur J Neurosci 36:3521-30. 2012
    ..In conclusion, prolonged systemic chemotherapy is associated with a decrease in hippocampal adult neurogenesis and theta activity that may explain the selective deficits in processes of learning that describe the 'chemobrain'...
  9. pmc Neurogenesis and the spacing effect: learning over time enhances memory and the survival of new neurons
    Helene M Sisti
    Department of Psychology and Center for Collaborative Neuroscience, Rutgers University, Piscataway, New Jersey, USA
    Learn Mem 14:368-75. 2007
    ..They also indicate that learning over an extended period of time induces a more persistent memory, which then relates to the number of cells that reside in the hippocampus...
  10. pmc Learning during motherhood: A resistance to stress
    Benedetta Leuner
    Department of Psychology and Center for Collaborative Neuroscience, Rutgers University, 152 Frelinghuysen Road, Piscataway, NJ 08854, USA
    Horm Behav 50:38-51. 2006
    ..Together, these data suggest that the presence of offspring and the nurturing and care-giving activities that they elicit protect females from the adverse effect of stress on processes involved in learning and memory...
  11. pmc Learning during middle age: a resistance to stress?
    Georgia E Hodes
    Department of Psychology and Center for Collaborative Neuroscience, Rutgers University, 152 Frelinghuysen Road, Piscataway, NJ 08854, United States
    Neurobiol Aging 28:1783-8. 2007
    ..Together, these data indicate that associative learning in the aging animal is resistant to both the negative and positive consequences of stressful experience...
  12. pmc Stressful experience and learning across the lifespan
    Tracey J Shors
    Department of Psychology, Center for Collaborative Neuroscience, Rutgers University, Piscataway, New Jersey 08854, USA
    Annu Rev Psychol 57:55-85. 2006
    ....
  13. pmc Prozac during puberty: distinctive effects on neurogenesis as a function of age and sex
    G E Hodes
    Department of Psychology and Center for Collaborative Neuroscience, Rutgers University, Piscataway, NJ 08854, USA
    Neuroscience 163:609-17. 2009
    ..Treatment of female rats with fluoxetine during puberty decreased circulating levels of corticosterone in adults, even in the absence of the drug suggesting disruption of maturation of the hypothalamic-pituitary-adrenal axis...
  14. pmc Critical brain circuits at the intersection between stress and learning
    Debra A Bangasser
    Department of Anesthesiology, The Children s Hospital of Philadelphia, Philadelphia, PA 19104, USA
    Neurosci Biobehav Rev 34:1223-33. 2010
    ....
  15. pmc Changing the rate and hippocampal dependence of trace eyeblink conditioning: slow learning enhances survival of new neurons
    Jaylyn Waddell
    University of Maryland, Baltimore, Department of Physiology, School of Medicine, 655 W Baltimore St, Baltimore, MD 21201, USA
    Neurobiol Learn Mem 95:159-65. 2011
    ..These data demonstrate that rate of acquisition and not hippocampal dependence determines the impact of learning on adult neurogenesis...
  16. pmc Learning increases the survival of newborn neurons provided that learning is difficult to achieve and successful
    Daniel M Curlik
    Department of Psychology and Center for Collaborative Neuroscience, Rutgers University, 152 Frelinghuysen Road, Piscataway, NJ 08854 8020, USA
    J Cogn Neurosci 23:2159-70. 2011
    ..Together, these results demonstrate that NMDA receptor activation modifies learning and as a consequence alters the number of surviving cells in the adult hippocampus...
  17. pmc Associative learning increases adult neurogenesis during a critical period
    Megan L Anderson
    Department of Neuroscience, Rutgers University, Piscataway, NJ 08854, USA
    Eur J Neurosci 33:175-81. 2011
    ..Overall, these results suggest the presence of a feedback system, which controls how many new neurons become incorporated into the adult brain in response to learning...
  18. pmc Use it or lose it: how neurogenesis keeps the brain fit for learning
    T J Shors
    Department of Psychology, Center for Collaborative Neuroscience, Rutgers University, Piscataway, NJ 08854, USA
    Behav Brain Res 227:450-8. 2012
    ..In this way, neurogenesis and learning interact to maintain a fit brain...
  19. pmc Rapid estrogen signaling in the brain: implications for the fine-tuning of neuronal circuitry
    Deepak P Srivastava
    Department of Physiology, Feinberg School of Medicine, Northwestern University, Chicago, Illinois 60611, USA
    J Neurosci 31:16056-63. 2011
    ....
  20. pmc Once a mother, always a mother: maternal experience protects females from the negative effects of stress on learning
    Lisa Y Maeng
    Department of Psychology, Rutgers University, Piscataway, NJ 08854, USA
    Behav Neurosci 126:137-41. 2012
    ..These data suggest that maternal experience induces a protective mechanism in mothers, which promotes associative learning long after the offspring have left their care...
  21. pmc Learning to learn: theta oscillations predict new learning, which enhances related learning and neurogenesis
    Miriam S Nokia
    Department of Psychology, Center for Collaborative Neuroscience, Rutgers University, Piscataway, New Jersey, United States of America
    PLoS ONE 7:e31375. 2012
    ..In conclusion, these data argue against an upper limit on the number of neurons that can be rescued from death by learning...
  22. pmc Significant life events and the shape of memories to come: a hypothesis
    Tracey J Shors
    Department of Psychology, Center for Collaborative Neuroscience, Rutgers University, USA
    Neurobiol Learn Mem 85:103-15. 2006
    ..It is proposed that these modulatory processes allow past experiences to change the shape of memories to come. In this way, memorable life events become less about the past and more about the future...
  23. pmc d-cycloserine reverses the detrimental effects of stress on learning in females and enhances retention in males
    Jaylyn Waddell
    Department of Psychology and Center for Collaborative Neuroscience, Rutgers University, Piscataway, NJ 08854, USA
    Neurobiol Learn Mem 93:31-6. 2010
    ..Thus, as shown previously, training in the presence of an NMDA receptor agonist enhances associative learning and memory retention. In addition, it can reverse learning deficits that have already been induced...
  24. pmc Neurogenesis and learning: acquisition and asymptotic performance predict how many new cells survive in the hippocampus
    Christina Dalla
    Department of Psychology and Center for Collaborative Neuroscience, Rutgers University, Piscataway, NJ 08854, USA
    Neurobiol Learn Mem 88:143-8. 2007
    ..These data support the idea that learning and not simply training increases the survival of the new cells in the hippocampus...
  25. pmc Sex differences in learning processes of classical and operant conditioning
    Christina Dalla
    Department of Psychology and Center for Collaborative Neuroscience, Rutgers University, Piscataway, New Jersey 08854, USA
    Physiol Behav 97:229-38. 2009
    ..Finally, we discuss how sex differences in learning continue to alter the brain throughout the lifespan. Thus, sex differences in learning are not only mediated by sex differences in the brain, but also contribute to them...
  26. pmc Neurogenesis and helplessness are mediated by controllability in males but not in females
    Tracey J Shors
    Department of Psychology and Center for Collaborative Neuroscience, Rutgers University, Piscataway, New Jersey 08854, USA
    Biol Psychiatry 62:487-95. 2007
    ..Here, we tested the hypothesis that uncontrollable but not controllable stress would reduce cell proliferation in the hippocampus of male and female rats and would relate to the expression of helplessness behavior...
  27. ncbi Females do not express learned helplessness like males do
    Christina Dalla
    Department of Psychology and Center for Collaborative Neuroscience, Rutgers University, Piscataway, NJ 08854, USA
    Neuropsychopharmacology 33:1559-69. 2008
    ..Learned helplessness may not constitute a valid model for depressive behavior in women, at least as reflected by the response of female rats to operant conditioning procedures after stressful experience...
  28. pmc Temporal discontiguity is neither necessary nor sufficient for learning-induced effects on adult neurogenesis
    Benedetta Leuner
    Department of Psychology, Princeton University, Princeton, New Jersey 08544, USA
    J Neurosci 26:13437-42. 2006
    ..Together, these results demonstrate that associative learning increases the survival of new neurons in the adult hippocampus, regardless of temporal contiguity...
  29. pmc Trace conditioning and the hippocampus: the importance of contiguity
    Debra A Bangasser
    Department of Psychology and Center for Collaborative Neuroscience, Rutgers University, Piscataway, New Jersey 08854, USA
    J Neurosci 26:8702-6. 2006
    ..Therefore, the dependence of traditional trace paradigms on the hippocampus can be attributed to the absence of temporal contiguity...
  30. pmc The basolateral nucleus of the amygdala is necessary to induce the opposing effects of stressful experience on learning in males and females
    Jaylyn Waddell
    Department of Psychology and Center for Collaborative Neuroscience, Rutgers University, Piscataway, New Jersey 08854, USA
    J Neurosci 28:5290-4. 2008
    ..Thus, the BLA is necessary to induce the long-term effect of stressful experience on conditioning regardless of sex and direction of modulation...
  31. pmc The bed nucleus of the stria terminalis modulates learning after stress in masculinized but not cycling females
    Debbie A Bangasser
    Department of Psychology and Center for Collaborative Neuroscience, Rutgers University, Piscataway, New Jersey 08854, USA
    J Neurosci 28:6383-7. 2008
    ..Importantly, together these studies indicate that males and females can engage different brain structures to modulate learning after a stressful experience...
  32. pmc Growth hormone is produced within the hippocampus where it responds to age, sex, and stress
    Christine P Donahue
    Department of Neurology, Harvard Medical School, Boston, MA 02115, USA
    Proc Natl Acad Sci U S A 103:6031-6. 2006
    ..These results suggest that GH may be involved in functions ascribed to the hippocampus, such as learning and the response to stressful experience...
  33. ncbi From stem cells to grandmother cells: how neurogenesis relates to learning and memory
    Tracey J Shors
    Department of Psychology, Rutgers University, Piscataway, NJ 08854, USA
    Cell Stem Cell 3:253-8. 2008
    ..This commentary considers how learning enhances the survival of neural stem/progenitor cell progeny and what these new neurons might do once they are rescued from death...
  34. pmc Female rats learn trace memories better than male rats and consequently retain a greater proportion of new neurons in their hippocampi
    Christina Dalla
    Department of Psychology and Center for Collaborative Neuroscience, Rutgers University, Piscataway, NJ 08854, USA
    Proc Natl Acad Sci U S A 106:2927-32. 2009
    ..Thus, sex differences in learning alter the anatomical structure of the hippocampus. As a result, male and female brains continue to differentiate in adulthood...
  35. ncbi Is there a link between adult neurogenesis and learning?
    Benedetta Leuner
    Department of Psychology, Princeton University, Princeton, New Jersey 08544, USA
    Hippocampus 16:216-24. 2006
    ..This review discusses both sides of this issue, considering the effects of learning on the production of new neurons in the dentate gyrus and the question of whether newly born cells participate in learning and memory...
  36. pmc Estrogen and learning: strategy over parsimony
    Tracey J Shors
    Learn Mem 12:84-5. 2005