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BDNF upregulation during declarative memory formation in monkey inferior temporal cortex

Nature Neuroscience volume 3, pages 1134–1142 (2000)Cite this article

Abstract

In primates, visual long-term memory of objects is presumably stored in the inferior temporal (IT) cortex. Because brain-derived neurotrophic factor (BDNF) is involved in activity-dependent neural reorganization, we tested the hypothesis that BDNF would be upregulated in IT cortex during formation of visual pair-association memory. To eliminate genetic and cognitive variations between individual animals, we used split-brain monkeys for intra-animal comparison in PCR-based mRNA quantitation. The monkeys learned a pair-association (PA) task using one hemisphere and a control visual task using the other, to balance the amount of visual input. We found that BDNF was upregulated selectively in area 36 of IT cortex during PA learning, but not in areas involved in earlier stages of visual processing. In situ hybridization showed that BDNF-expressing cells were localized in a patchlike cluster. The results suggest that BDNF contributes to reorganization of neural circuits for visual long-term memory formation in the primate.

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Figure 1: Visual memory tasks for split-brain monkeys.
Figure 2: Sequential learning with three sets of visual stimuli.
Figure 3: Monkey cortical areas for RNA extraction.
Figure 4: PCR coamplification of the BDNF gene with an internal standard gene in single reaction tubes.
Figure 5: Intra-animal comparison of mRNA expression levels in the two visual memory tasks.
Figure 6: In situ hybridization of BDNF mRNA.

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References

  1. Squire, L. R. & Zola-Morgan, S. The medial temporal lobe memory system. Science 253, 1380–1386 (1991).

    Article  CAS  Google Scholar 

  2. Mishkin, M., Suzuki, W. A., Gadian, D. G. & Vargha-Khadem, F. Hierarchical organization of cognitive memory. Phil. Trans. R. Soc. Lond. B Biol. Sci. 352, 1461–1467 (1997).

    Article  CAS  Google Scholar 

  3. Jones, E. G. Cortical and subcortical contributions to activity-dependent plasticity in primate somatosensory cortex. Annu. Rev. Neurosci. 23, 1–37 (2000).

    Article  CAS  Google Scholar 

  4. Martin, S. J., Grimwood, P. D. & Morris, R. G. Synaptic plasticity and memory: an evaluation of the hypothesis. Annu. Rev. Neurosci. 23, 649–711 (2000).

    Article  CAS  Google Scholar 

  5. Miyashita, Y. Inferior temporal cortex: where visual perception meets memory. Annu. Rev. Neurosci. 16, 245–263 (1993).

    Article  CAS  Google Scholar 

  6. Wechsler, D. Wechsler Memory Scale Revisited (The Psychological Corporation, Harcourt Brace Jovanovich, San Antonio, Texas, 1987).

    Google Scholar 

  7. Sakai, K. & Miyashita, Y. Neural organization for the long-term memory of paired associates. Nature 354, 152–155 (1991).

    Article  CAS  Google Scholar 

  8. Murray, E. A., Gaffan, D. & Mishkin, M. Neural substrates of visual stimulus–stimulus association in rhesus monkeys. J. Neurosci. 13, 4549–4561 (1993).

    Article  CAS  Google Scholar 

  9. Miyashita, Y. & Hayashi, T. Neural representation of visual objects: encoding and top-down activation. Curr. Opin. Neurobiol. 10, 187–194 (2000).

    Article  CAS  Google Scholar 

  10. Rolls, E. T. Learning mechanisms in the temporal lobe visual cortex. Behav. Brain Res. 66, 177–185 (1995).

    Article  CAS  Google Scholar 

  11. Erickson, C. A. & Desimone, R. Responses of macaque perirhinal neurons during and after visual stimulus association learning. J. Neurosci. 19, 10404–10416 (1999).

    Article  CAS  Google Scholar 

  12. Aggleton, J. P. & Brown, M. W. Episodic memory, amnesia, and the hippocampal–anterior thalamic axis. Behav. Brain Sci. 22, 425–489 (1999).

    CAS  PubMed  Google Scholar 

  13. Buckley, M. J. & Gaffan, D. Perirhinal cortex ablation impairs configural learning and paired-associate learning equally. Neuropsychologia 36, 535–546 (1998).

    Article  CAS  Google Scholar 

  14. Liu, Z. & Richmond, B. J. Response differences in monkey TE and perirhinal cortex: stimulus association related to reward schedules. J. Neurophysiol. 83, 1677–1692 (2000).

    Article  CAS  Google Scholar 

  15. Bonhoeffer, T. Neurotrophins and activity-dependent development of the neocortex. Curr. Opin. Neurobiol. 6, 119–126 (1996).

    Article  CAS  Google Scholar 

  16. Lewin, G. R. & Barde, Y. A. Physiology of the neurotrophins. Annu. Rev. Neurosci. 19, 289–317 (1996).

    Article  CAS  Google Scholar 

  17. Thoenen, H. Neurotrophins and neuronal plasticity. Science 270, 593–598 (1995).

    Article  CAS  Google Scholar 

  18. McAllister, A. K., Katz, L. C. & Lo, D. C. Neurotrophins and synaptic plasticity. Annu. Rev. Neurosci. 22, 295–318 (1999).

    Article  CAS  Google Scholar 

  19. Cabelli, R. J., Shelton, D. L., Segal, R. A. & Shatz, C. J. Blockade of endogenous ligands of TrkB inhibits formation of ocular dominance columns. Neuron 19, 63–76 (1997).

    Article  CAS  Google Scholar 

  20. Hanover, J. L., Huang, Z. J., Tonegawa, S. & Stryker, M. P. Brain-derived neurotrophic factor overexpression induces precocious critical period in mouse visual cortex. J. Neurosci. 19, RC40 (1999).

    Article  CAS  Google Scholar 

  21. Castren, E., Zafra, F., Thoenen, H. & Lindholm, D. Light regulates expression of brain-derived neurotrophic factor mRNA in rat visual cortex. Proc. Natl. Acad. Sci. USA 89, 9444–9448 (1992).

    Article  CAS  Google Scholar 

  22. Patterson, S. L., Grover, L. M., Schwartzkroin, P. A. & Bothwell, M. Neurotrophin expression in rat hippocampal slices: a stimulus paradigm inducing LTP in CA1 evokes increases in BDNF and NT-3 mRNAs. Neuron 9, 1081–1088 (1992).

    Article  CAS  Google Scholar 

  23. Hasegawa, I., Fukushima, T., Ihara, T. & Miyashita, Y. Callosal window between prefrontal cortices: cognitive interaction to retrieve long-term memory. Science 281, 814–818 (1998).

    Article  CAS  Google Scholar 

  24. Tomita, H., Ohbayashi, M., Nakahara, K., Hasegawa, I. & Miyashita, Y. Top-down signal from prefrontal cortex in executive control of memory retrieval. Nature 401, 699–703 (1999).

    Article  CAS  Google Scholar 

  25. Gazzaniga, M. S. Principles of human brain organization derived from split-brain studies. Neuron 14, 217–228 (1995).

    Article  CAS  Google Scholar 

  26. Zola-Morgan, S., Squire, L. R., Amaral, D. G. & Suzuki, W. A. Lesions of perirhinal and parahippocampal cortex that spare the amygdala and hippocampal formation produce severe memory impairment. J. Neurosci. 9, 4355–4370 (1989).

    Article  CAS  Google Scholar 

  27. Okuno, H. & Miyashita, Y. Expression of the transcription factor Zif268 in the temporal cortex of monkeys during visual paired associate learning. Eur. J. Neurosci. 8, 2118–2128 (1996).

    Article  CAS  Google Scholar 

  28. Gause, W. C. & Adamovicz, J. in PCR Primer: a Laboratory Manual (eds. Dieffenbach, C. W. & Dveksler, G. S.) 293–311 (Cold Spring Harbor Laboratory Press, Cold Spring Harbor, New York, 1995).

    Google Scholar 

  29. Okuno, H., Tokuyama, W., Li, Y. X., Hashimoto, T. & Miyashita, Y. Quantitative evaluation of neurotrophin and trk mRNA expression in visual and limbic areas along the occipito–temporo–hippocampal pathway in adult macaque monkeys. J. Comp. Neurol. 408, 378–398 (1999).

    Article  CAS  Google Scholar 

  30. Tokuyama, W., Hashimoto, T., Li, Y. X., Okuno, H. & Miyashita, Y. Highest trk B mRNA expression in the entorhinal cortex among hippocampal subregions in the adult rat: contrasting pattern with BDNF mRNA expression. Mol. Brain Res. 62, 206–215 (1998).

    Article  CAS  Google Scholar 

  31. Barbacid, M. The Trk family of neurotrophin receptors. J. Neurobiol. 25, 1386–1403 (1994).

    Article  CAS  Google Scholar 

  32. Huntley, G. W., Benson, D. L., Jones, E. G. & Isackson, P. J. Developmental expression of brain derived neurotrophic factor mRNA by neurons of fetal and adult monkey prefrontal cortex. Dev. Brain Res. 70, 53–63 (1992).

    Article  CAS  Google Scholar 

  33. Hashimoto, T., Okuno, H., Tokuyama, W., Li, Y. X. & Miyashita, Y. Expression of brain-derived neurotrophic factor, neurotrophin-3 and their receptor messenger RNAs in monkey rhinal cortex. Neuroscience 95, 1003–1010 (2000).

    Article  CAS  Google Scholar 

  34. Kawamoto, Y., Nakamura, S., Kawamata, T., Akiguchi, I. & Kimura, J. Cellular localization of brain-derived neurotrophic factor-like immunoreactivity in adult monkey brain. Brain Res. 821, 341–349 (1999).

    Article  CAS  Google Scholar 

  35. Dragunow, M., Hughes, P., Mason-Parker, S. E., Lawlor, P. & Abraham, W. C. TrkB expression in dentate granule cells is associated with a late phase of long-term potentiation. Mol. Brain Res. 46, 274–280 (1997).

    Article  CAS  Google Scholar 

  36. Hughes, P., Beilharz, E., Gluckman, P. & Dragunow, M. Brain-derived neurotrophic factor is induced as an immediate early gene following N-methyl-D-aspartate receptor activation. Neuroscience 57, 319–328 (1993).

    Article  CAS  Google Scholar 

  37. Zafra, F., Hengerer, B., Leibrock, J., Thoenen, H. & Lindholm, D. Activity dependent regulation of BDNF and NGF mRNAs in the rat hippocampus is mediated by non-NMDA glutamate receptors. EMBO J. 9, 3545–3550 (1990).

    Article  CAS  Google Scholar 

  38. Falkenberg, T., Ernfors, P., Persson, H. & Lindefors, N. Cortical transynaptic activation of tyrosine kinase receptor trkB messenger RNA expression in rat hippocampus. Neuroscience 51, 883–889 (1992).

    Article  CAS  Google Scholar 

  39. Stone, J., Leicester, J. & Sherman, S. M. The naso-temporal division of the monkey's retina. J. Comp. Neurol. 150, 333–348 (1973).

    Article  CAS  Google Scholar 

  40. Fendrich, R. & Gazzaniga, M. S. Evidence of foveal splitting in a commissurotomy patient. Neuropsychologia 27, 273–281 (1989).

    Article  CAS  Google Scholar 

  41. Sugishita, M., Hamilton, C. R., Sakuma, I. & Hemmi, I. Hemispheric representation of the central retina of commissurotomized subjects. Neuropsychologia 32, 399–415 (1994).

    Article  CAS  Google Scholar 

  42. Neeper, S. A., Gomez-Pinilla, F., Choi, J. & Cotman, C. Exercise and brain neurotrophins. Nature 373, 109 (1995).

    Article  CAS  Google Scholar 

  43. Xiang, J. Z. & Brown, M. W. Differential neuronal responsiveness in primate perirhinal cortex and hippocampal formation during performance of a conditional visual discrimination task. Eur. J. Neurosci. 11, 3715–3724 (1999).

    Article  CAS  Google Scholar 

  44. Gaffan, D. & Harrison, S. Auditory–visual associations, hemispheric specialization and temporal–frontal interaction in the rhesus monkey. Brain 114, 2133–2144 (1991).

    Article  Google Scholar 

  45. Higuchi, S. & Miyashita, Y. Formation of mnemonic neuronal responses to visual paired associates in inferotemporal cortex is impaired by perirhinal and entorhinal lesions. Proc. Natl. Acad. Sci. USA 93, 739–743 (1996).

    Article  CAS  Google Scholar 

  46. Buckley, M. J. & Gaffan, D. Impairment of visual object-discrimination learning after perirhinal cortex ablation. Behav. Neurosci. 111, 467–475 (1997).

    Article  CAS  Google Scholar 

  47. Buffalo, E. A. et al. Dissociation between the effects of damage to perirhinal cortex and area TE. Learn. Mem. 6, 572–599 (1999).

    Article  CAS  Google Scholar 

  48. Eacott, M. J., Gaffan, D. & Murray, E. A. Preserved recognition memory for small sets, and impaired stimulus identification for large sets, following rhinal cortex ablations in monkeys. Eur. J. Neurosci. 6, 1466–1478 (1994).

    Article  CAS  Google Scholar 

  49. Tokuyama, W., Hashimoto, T., Li, Y. X., Okuno, H. & Miyashita, Y. Quantification of neurotrophin-3 mRNA in the rat hippocampal subregions using the RT-PCR-based coamplification method. Brain Res. Protoc. 4, 407–414 (1999).

    Article  CAS  Google Scholar 

  50. Van Essen, D. C., Newsome, W. T. & Maunsell, J. H. The visual field representation in striate cortex of the macaque monkey: asymmetries, anisotropies, and individual variability. Vision Res. 24, 429–448 (1984).

    Article  CAS  Google Scholar 

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Acknowledgements

This work was supported by a Grant-in-Aid for Specially Promoted Research (07102006) to Y. M. and by a Grant-in-Aid for Encouragement of Young Scientists (11780574) to H. O. from the Japanese Ministry of Education, Science, Sports, and Culture.

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Author notes

  1. Wataru Tokuyama and Hiroyuki Okuno: The first two authors contributed equally to this work

Authors and Affiliations

  1. Department of Physiology, University of Tokyo School of Medicine, Hongo 7-3-1, Bunkyo-ku, 113-0033, Tokyo, Japan

    Wataru Tokuyama, Hiroyuki Okuno & Yasushi Miyashita

  2. Mind Articulation Project, ICORP, Japan Science and Technology Corporation, Yushima 4-9-2, 113-0034, Tokyo, Bunkyo-ku, Japan

    Takanori Hashimoto, Yue Xin Li & Yasushi Miyashita

  3. National Institute for Physiological Sciences, Myodaiji 38, Okazaki, 444-8585, Aichi, Japan

    Yasushi Miyashita

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Correspondence to Yasushi Miyashita.

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Tokuyama, W., Okuno, H., Hashimoto, T. et al. BDNF upregulation during declarative memory formation in monkey inferior temporal cortex. Nat Neurosci 3, 1134–1142 (2000). https://doi.org/10.1038/80655

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