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Learning enhances adult neurogenesis in the hippocampal formation

Abstract

Thousands of hippocampal neurons are born in adulthood, suggesting that new cells could be important for hippocampal function. To determine whether hippocampus-dependent learning affects adult-generated neurons, we examined the fate of new cells labeled with the thymidine analog bromodeoxyuridine following specific behavioral tasks. Here we report that the number of adult-generated neurons doubles in the rat dentate gyrus in response to training on associative learning tasks that require the hippocampus. In contrast, training on associative learning tasks that do not require the hippocampus did not alter the number of new cells. These findings indicate that adult-generated hippocampal neurons are specifically affected by, and potentially involved in, associative memory formation.

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Figure 1: Learning that requires the hippocampus, but not other types of learning or a similar experience in the absence of overt learning, increased the numbers of adult-generated hippocampal granule neurons.
Figure 2: The number of new neurons in the granule cell layer (Gcl) of adult rats increases following spatial learning in the Morris water maze.

References

  1. Milner, B. Disorders of learning and memory after temporal lobe lesions in man. Clin. Neurosurg. 19, 421–446 (1972).

    Article  CAS  Google Scholar 

  2. Squire, L. R. The neuropsychology of human memory. Annu. Rev. Neurosci. 5, 241–273 (1982).

    Article  CAS  Google Scholar 

  3. Barnea, A. & Nottebohm, F. Seasonal recruitment of hippocampal neurons in adult free-ranging black-capped chickadees. Proc. Natl. Acad. Sci. USA 8, 11217–11221 (1994).

    Article  Google Scholar 

  4. Bayer, S. A. Changes in the total number of dentate granule cells in juvenile and adult rats: a correlated volumetric and 3H-thymidine autoradiographic study. Exp. Brain. Res. 46, 315– 323 (1982).

    Article  CAS  Google Scholar 

  5. Cameron, H. A., Woolley, C. S., McEwen, B. S. & Gould, E. Differentiation of newly born neurons and glia in the dentate gyrus of the adult rat. Neuroscience 56, 337– 344 (1993).

    Article  CAS  Google Scholar 

  6. Kempermann, G., Kuhn, H. G. & Gage, F. H. More hippocampal neurons in adult mice living in an enriched environment. Nature 386, 493– 495 (1997).

    Article  CAS  Google Scholar 

  7. Gould, E., McEwen, B. S., Tanapat, P., Galea, L. A. M. & Fuchs, E. Neurogenesis in the dentate gyrus of the adult tree shrew is regulated by psychosocial stress and NMDA receptor activation. J. Neurosci. 17, 2492– 2498 (1997).

    Article  CAS  Google Scholar 

  8. Gould, E., Tanapat, P., McEwen, B. S., Flugge, G. & Fuchs, E. Proliferation of granule cell precursors in the dentate gyrus of adult monkeys is diminished by stress. Proc. Natl. Acad. Sci. USA 95, 3168– 3171 (1998).

    Article  CAS  Google Scholar 

  9. Solomon, P. R., Vander Schaaf, E. R., Weisz, D. J. & Thompson, R. F. Hippocampus and trace conditioning of the rabbit's classically conditioned nictitating membrane response. Neuroscience 100, 729–744 (1986).

    CAS  Google Scholar 

  10. Moyer, J. R., Deyo, R. A. & Disterhoft, J. F. Hippocampectomy disrupts trace eye-blink conditioning in rabbits. Behav. Neurosci., 104, 243– 252 (1990).

    Article  Google Scholar 

  11. Weiss, C., Bouwmeester, H., Power, J. & Disterhoft, J. F. Hippocampal lesions prevent trace eyeblink conditioning in the freely moving rat. Behav. Brain Res. (in press).

  12. Clark, R. E. & Squire, L. R . Classical conditioning and brain systems: the role of awareness. Science 280, 77–81 (1998).

    Article  CAS  Google Scholar 

  13. Morris, R. G. M., Garrud, P., Rawlins, J. N. P. & O'Keefe, J. Place navigation is impaired in rats with hippocampal lesions. Nature, 297, 681–683 ( 1982).

    Article  CAS  Google Scholar 

  14. Kuhn, H. G., Dickinson-Anson, H. & Gage, F. H. Neurogenesis in the dentate gyrus of the adult rat: age-related decrease of neuronal progenitor proliferation. J. Neurosci. 16, 2027–2033 ( 1996).

    Article  CAS  Google Scholar 

  15. Gould, E., Woolley, C. S. & McEwen, B. S. Short-term glucocorticoid manipulations affect neuronal morphology and survival in the adult dentate gyrus. Neuroscience 37, 367–375 ( 1990).

    Article  CAS  Google Scholar 

  16. Weisz, D., Clark, G. A. & Thompson, R. F. Increased responsivity of dentate granule cells during nictitating membrane response conditioning in the rabbit. Behav. Brain Res. 12, 145–154 ( 1984).

    Article  CAS  Google Scholar 

  17. Shapiro, M. L., Tanila, H. & Eichenbaum, H. Cues that hippocampal place cells encode: dynamic and hierarchical representation of local and distal stimuli. Hippocampus 7, 624–642 ( 1997).

    Article  CAS  Google Scholar 

  18. Gould, E., Cameron, H. A., Daniels, D. C., Woolley, C. S. & McEwen, B. S. Adrenal hormones suppress cell division in the adult rat dentate gyrus. J. Neurosci. 12, 3642–3650 (1992).

    Article  CAS  Google Scholar 

  19. Cameron, H. A., Tanapat, P. & Gould, E. Adrenal steroids and N-methyl-D-aspartate receptor activation regulate neurogenesis in the dentate gyrus of adult rats through a common pathway. Neuroscience 82, 349– 354 (1998).

    Article  CAS  Google Scholar 

  20. Moghaddam, B. & Bolinao, M. L., Stein-Behrens, B. & Sapolsky, R. Glucocorticoids mediate the stress-induced extracellular accumulation of glutamate. Brain Res. 655, 251–254 (1994).

    Article  CAS  Google Scholar 

  21. Cameron, H. A. & Gould, E. Distinct populations of cells in the adult dentate gyrus undergo mitosis or apoptosis in response to adrenalectomy. J. Comp. Neurol. 369, 56–63 (1996).

    Article  CAS  Google Scholar 

  22. Krugers, H. J. et al. Exposure to chronic psychosocial stress and corticosterone in the rat: effects on spatial discrimination learning and hippocampal protein kinase Cgamma immunoreactivity. Hippocampus 7, 427–436 (1997).

    Article  CAS  Google Scholar 

  23. Bodnoff, S. R. et al. Enduring effects of chronic corticosterone treatment on spatial learning, synaptic plasticity, and hippocampal neuropathology in young and mid-aged rats. J. Neurosci. 15, 61– 69 (1995).

    Article  CAS  Google Scholar 

  24. Wallenstein, G. V., Eichenbaum, H. & Hasselmo, M. E. The hippocampus as an associator of discontiguous events. Trends Neurosci. 21, 317– 323 (1998).

    Article  CAS  Google Scholar 

  25. Squire, L. R. & Zola, S. M. Amnesia, memory and brain systems. Phil. Trans. R. Soc. Lond. B 352,1663– 1673 (1997).

    Article  CAS  Google Scholar 

  26. Shors, T. J. & Mathew, P. R. NMDA receptor antagonism in the lateral/basolateral but not central nucleus of the amygdala prevents the induction of facilitated learning in response to stress. Learn. Mem. 5, 220–225 (1998).

    CAS  PubMed  PubMed Central  Google Scholar 

  27. Beylin, A. V. & Shors, T. J. Stress enhances excitatory trace eyeblink conditioning and opposes acquisition of inhibitory conditioning. Behav. Neurosci. 112, 1327– 1338 (1998).

    Article  CAS  Google Scholar 

  28. Schmaltz, L. W. & Theios, J. Acquisition and extinction of a classically conditioned response in hippocampectomized rabbits. J. Comp. Physiol. Psychol. 79, 328– 333 (1972).

    Article  CAS  Google Scholar 

  29. Markowska, A. L., Long, J. M., Johnson, C. T. & Olton, D. S. Variable-interval probe test as a tool for repeated measurements of spatial memory in the water maze. Behav. Neurosci. 107, 627–632 (1993).

    Article  CAS  Google Scholar 

  30. McCormick, C. M., McNamara, M., Mukhopadhyay, S. & Kelsey, J. E. Acute corticosterone replacement reinstates performance on spatial and nonspatial memory tasks 3 months after adrenalectomy despite degeneration in the dentate gyrus. Behav. Neurosci. 111, 518– 531 (1997).

    Article  CAS  Google Scholar 

  31. Minturn, J. E., Geschwind, D. H., Fryer, H. J. & Hockfield, S. Early postmitotic neurons transiently express TOAD-64, a neural specific protein. J. Comp. Neurol. 355, 369– 379 (1995).

    Article  CAS  Google Scholar 

  32. West, M. J., Slomianka, L. & Gundersen, H. J. G. Unbiased stereological estimation of the total number of neurons in the subdivisions of the rat hippocampus using the optical fractionator. Anat. Rev. 231, 482– 497 (1991).

    Article  CAS  Google Scholar 

  33. Gundersen, H. J. G. et al. Some new, simple and efficient stereological methods and their use in pathological research and diagnosis. APMIS 96 , 379–394 (1988).

    Article  CAS  Google Scholar 

  34. Van Praag, H., Kempermann, G. & Gage, F. H. Running increases cell proliferation and neurogenesis in the adult mouse dentate gyrus. Nat. Neurosci. 2, 266–270 (1999).

    Article  CAS  Google Scholar 

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Acknowledgements

We thank Charles Gross for comments on the manuscript and Joseph Goodhouse for assistance with confocal imaging. This work was supported by MH52423, MH59970 and IBN9511027.

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Correspondence to Elizabeth Gould.

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Gould, E., Beylin, A., Tanapat, P. et al. Learning enhances adult neurogenesis in the hippocampal formation. Nat Neurosci 2, 260–265 (1999). https://doi.org/10.1038/6365

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