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Stable and Unstable Activation of the Prefrontal Cortex with Dopaminergic Modulation

  • Shoji Tanaka

The so-called inverted-U shaped profile of the dependence of working memory performance on D1 receptor activation in the prefrontal cortex (PFC) illustrates how the cognitive function declines with the deviation of the dopamine (DA) level in the PFC from the optimum point. A recent computational study, however, suggests that the PFC circuit is not always stable along the inverted-U shaped curve. This is due to effectively positive feedback control of the prefronto-mesoprefrontal system under hypodopaminergic conditions. The instability of the PFC circuit makes the activity of the PFC largely fluctuating. Because of this, even a slight increase in DA releasability causes a catastrophic jump of the activity of the PFC from a low to a high level. Under hyperdopaminergic conditions, in contrast, the PFC circuit is stable by means of negative feedback control. This chapter reviews these computational studies and argues the stable and unstable activation of the PFC in connection with cognitive deficits observed in schizophrenia.

Keywords

Prefrontal Cortex Pyramidal Neuron Work Memory Performance Stable Fixed Point Unstable Fixed Point 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.

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References

  1. Abi-Dargham, A., Mawlawi, O., Lombardo, I., Gil, R., Martinez, D., Huang, Y., Hwang, D.-R., Keilp, J., Kochan, L., Heertum, R. V., Gorman, J. M. and Laruelle, M. (2002) Prefron-tal dopamine D1 receptors and working memory in schizophrenia. J. Neurosci. 22, 3708-3719.PubMedGoogle Scholar
  2. Andreasen, N., Rezai, K., Alliger, R., Swayze II V., Flaum, M., Kirchner, P., Cohen, G. and O’Leary, D. S. (1992) Hypofrontality in neuroleptic-naive patients and in patients with chronic schizophrenia. Assessment with xenon 133 single-photon emission computed tomography and the Tower of London. Arch. Gen. Psychiatry. 49, 943-958.PubMedGoogle Scholar
  3. Benes, F. M. and Berretta, S. (2001) GABAergic interneurons: implications for understanding schizophrenia and bipolar disorder. Neuropsychopharmacology. 25, 1-27.CrossRefPubMedGoogle Scholar
  4. Brozoski, T. J., Brown, R. M., Rosvold, H. E. and Goldman, P. S. (1979) Cognitive deficit caused by regional depletion of dopamine in prefrontal cortex of rhesus monkey. Science. 205, 929-932.CrossRefPubMedGoogle Scholar
  5. Brunel, N. and Wang, X.-J. (2001) Effects of neuromodulation in a cortical network model of object working memory dominated by recurrent inhibition. J. Comput. Neurosci. 11, 63-85.CrossRefPubMedGoogle Scholar
  6. Callicott, J. H., Bertolino, A., Mattay, V. S., Langheim, F. J., Duyn, J., Coppola, R., Goldberg, T. E. and Weinberger, D. R. (2000) Physiological dysfunction of the dorsolateral prefrontal cortex in schizophrenia revisited. Cereb. Cortex. 10, 1078-1092.CrossRefPubMedGoogle Scholar
  7. Callicott, J. H., Mattay, V. S., Verchinski, B. A., Marenco, S., Egan, M. F. and Weinberger, D. R. (2003) Complexity of prefrontal cortical dysfunction in schizophrenia: more than up or down. Am. J. Psychiatry. 160, 2209-2215.CrossRefPubMedGoogle Scholar
  8. Carter, C. S., Perlstein, P., Ganguli, R., Brar, J., Mintun, M. and Cohen, J. D. (1998) Func-tional hypofrontality and working memory dysfunction in schizophrenia. Am. J. Psychia-try. 155, 1285-1287.Google Scholar
  9. Davis, K. L., Kahn, R. S., Ko, G. and Davidson, M. (1991) Dopamine in schizophrenia: a review and reconceptualization. Am. J. Psychiatry. 148, 1474-1486.PubMedGoogle Scholar
  10. Durstewitz, D., Seamans, J. K. and Sejnowski, T. J. (2000) Dopamine-mediated stabilization of delay-period activity in a network model of prefrontal cortex. J. Neurophysiol. 83, 1733-1750.PubMedGoogle Scholar
  11. Durstewitz, D. and Seamans, J. K. (2002) The computational role of dopamine D1 receptors in working memory. Neural Netw. 15, 561-572.CrossRefPubMedGoogle Scholar
  12. Elvevag, B. and Goldberg, T. E. (2000) Cognitive impairment in schizophrenia is the core of the disorder. Crit. Rev. Neurobiol. 14, 1-21.PubMedGoogle Scholar
  13. Frankle, W. G., Laruelle, M. and Haber, S. N. (2006) Prefrontal cortical projections to the midbrain in primates: evidence for a sparse connection. Neuropsychopharmacology 31, 1627-1636.CrossRefPubMedGoogle Scholar
  14. Funahashi, S., Bruce, C. J. and Goldman-Rakic, P. S. (1989) Mnemonic coding of visual space in the monkey’s dorsolateral prefrontal cortex. J. Neurophysiol. 61, 331-349.PubMedGoogle Scholar
  15. Fuster, J. M. (1997) The prefrontal cortex, third edition. Lippincott-Raven. Philadelphia, New York.Google Scholar
  16. Goldberg, T. E., David, A. and Gold, J. M. (2003) Neurocognitive deficits in schizophrenia. In: Hirsch SR and Weinberger DR (Eds.) Schizophrenia, 2e. Blackwell, Malden, MA, pp. 168-184.CrossRefGoogle Scholar
  17. Goldman-Rakic, P. S. (1987) Circuitry of primate prefrontal cortex and regulation of behavior by representational memory. Handbook of physiology, Sec 1: The nervous system, Vol V: Higher functions of the brain, Part 1. American Physiological Society, Bethesda, MD, 373-417.Google Scholar
  18. Goldman-Rakic, P. S. (1994) Working memory dysfunction in schizophrenia. J. Neuropsy-chiatry Clin. Neurosci. 6, 348-357.Google Scholar
  19. Grace, A. A. (1995) The tonic/phasic model of dopamine system regulation: its relevance for understanding how stimulant abuse can alter basal ganglia function. Drug Alcohol Depend. 37, 111-129.CrossRefPubMedGoogle Scholar
  20. Guo, N., Hwang, D. R., Lo, E. S., Huang, Y. Y., Laruelle, M. and Abi-Dargham, A. (2003) Dopamine depletion and in vivo binding of PET D1 receptor radioligands: implications for imaging studies in schizophrenia. Neuropsychopharmacology. 28, 1703-1711.CrossRefPubMedGoogle Scholar
  21. Kahn, R. S. and Davis, K. L. (2000) New Developments in Dopamine and Schizophrenia. Psychopharmacology: The Fourth Generation of Progress. http://www.acnp.org/G4/ GN401000115/CH113.html.
  22. Khalil, H. K. (2000) Nonlinear systems, third edition. Prentice-Hall: Upper Saddle River, NJ.Google Scholar
  23. Kuperberg, G. and Heckers, S. (2000) Schizophrenia and cognitive function. Curr. Opin. Neurobiol. 10, 205-210.CrossRefPubMedGoogle Scholar
  24. Laruelle, M. (2000) Imaging synaptic neurotransmission with in vivo binding competition techniques: a critical review. J Cereb. Blood Flow Metab. 20, 423-451.CrossRefPubMedGoogle Scholar
  25. Lewis, D. A., Hashimoto, T. and Volk, D. W. (2005) Cortical inhibitory neurons and schizo-phrenia. Nat. Rev. Neurosci. 6, 312-324.CrossRefPubMedGoogle Scholar
  26. Lewis, R. (2004) Should cognitive deficit be a diagnostic criterion for schizophrenia? J. Psy-chiatry Neurosci. 29, 102-113.Google Scholar
  27. Manoach, D. S. (2003) Prefrontal cortex dysfunction during working memory performance in schizophrenia: reconciling discrepant findings. Schizophr. Res. 60, 285-298.CrossRefPubMedGoogle Scholar
  28. Manoach, D. S., Gollub, R. L., Benson, E. S., Searl, M. M., Goff, D. C., Halpern, E., Saper, C. B. and Rauch, S. L. (2000) Schizophrenic subjects show aberrant fMRI activation of dorsolateral prefrontal cortex and basal ganglia during working memory performance. Biol. Psychiatry. 48, 99-109.CrossRefPubMedGoogle Scholar
  29. Manoach, D. S., Press, D. Z., Thangaraj, V., Searl, M. M., Goff, D. C., Halpern, E., Saper, C. B. and Warach, S. (1999) Schizophrenic subjects activate dorsolateral prefrontal cortex during a working memory task, as measured by fMRI. Biol. Psychiatry. 45, 1128-1137.CrossRefPubMedGoogle Scholar
  30. Meyer-Lindenberg, A., Miletich, R. S., Kohn, P. D., Esposito, G., Carson, R. E., Quarantelli, M., Weinberger, D. R. and Berman, K. F. (2002) Reduced prefrontal activity predicts exaggerated striatal dopaminergic function in schizophrenia. Nat. Neurosci. 5, 267-271.CrossRefPubMedGoogle Scholar
  31. Okubo, Y., Suhara, T., Suzuki, K., Kobayashi, K., Inoue, O., Terasaki, O., Someya, Y., Sassa, T., Sudo, Y., Matsushima, E., Iyo, M., Tateno, Y. and Toru, M. (1997) Decreased prefron-tal dopamine D1 receptors in schizophrenia revealed by PET. Nature. 385, 634-636.CrossRefPubMedGoogle Scholar
  32. Paquet, M., Tremblay, M., Soghomonian, J.-J. and Smith, Y. (1997) AMPA and NMDA glutamate receptor subunits in midbrain dopaminergic neurons in the squirrel monkey: an immunohistochemical and in situ hybridization study. J. Neurosci. 17, 1377-1396.PubMedGoogle Scholar
  33. Park, S. and Holzman, P. S. (1992) Schizophrenics show spatial working memory deficits. Arch. Gen. Psychiatry. 49, 975-982.PubMedGoogle Scholar
  34. Paulman, R. G., Devous, M. D., Sr., Gregory, R. R., Herman, J. H., Jennings, L., Bonte, F. J., Nasrallah, H. A., Raese, J. D. (1990) Hypofrontality and cognitive impairment in schizo-phrenia: dynamic single-photon tomography and neuropsychological assessment of schizophrenic brain function. Biol. Psychiatry. 27, 377-399.CrossRefPubMedGoogle Scholar
  35. Ramsey, N. F., Koning, H. A., Welles, P., Cahn, W., van der Linden, J. A. and Kahn, R. S. (2002) Excessive recruitment of neural systems subserving logical reasoning in schizo-phrenia. Brain. 125, 1793-1807.CrossRefPubMedGoogle Scholar
  36. Reynolds, G. P., Zhang, Z. J. and Beasley, C. L. (2001) Neurochemical correlates of cortical GABAergic deficits in schizophrenia: selective losses of calcium binding protein immuno-reactivity. Brain Res. Bull. 55, 579-584.Google Scholar
  37. Sesack, S. R. and Carr, D. B. (2002) Selective prefrontal cortex inputs to dopamine cells: implications for schizophrenia. Physiol. Behav. 77, 513-517.CrossRefPubMedGoogle Scholar
  38. Sesack, S. R., Carr, D. B., Omelchenko, N. and Pinto, A. (2003) Anatomical substrates for glutamate-dopamine interactions: evidence for specificity of connections and extrasynap-tic actions. Ann. N. Y. Acad. Sci. 1003, 36-52.CrossRefPubMedGoogle Scholar
  39. Tanaka, S. (2002a) Dopamine controls fundamental cognitive operations of multi-target spatial working memory. Neural Netw. 15, 573-582.CrossRefPubMedGoogle Scholar
  40. Tanaka, S. (2002b) Multi-directional representation of spatial working memory in a model prefrontal cortical circuit. Neurocomputing. 44-46, 1001-1008.CrossRefGoogle Scholar
  41. Tanaka, S. (2006) Dopaminergic control of working memory and its relevance to schizo-phrenia: a circuit dynamics perspective. Neuroscience. 139, 153-171.CrossRefPubMedGoogle Scholar
  42. Tzschentke, T. M. (2001) Pharmacology and behavioral pharmacology of the mesocortical dopamine system. Prog. Neurobiol. 63, 241-320.CrossRefPubMedGoogle Scholar
  43. Weinberger, D. R., Egan, M. F., Bertolino, A., Callicott, J. H., Mattay, V. S., Lipska, B. K., Berman, K. F. and Goldberg, T. E. (2001) Prefrontal neurons and the genetics of schizo-phrenia. Biol. Psychiatry. 50, 825-844.CrossRefPubMedGoogle Scholar
  44. Weinberger, D. R. and Laruelle, M. (2002) Neurochemical And Neuropharmacological Imag-ing In Schizophrenia. In: Kenneth L Davis, Dennis Charney, Joseph T Coyle, and Charles Nemeroff (Eds.), Neuropsychopharmacology: The Fifth Generation of Progress. Lippin-cott Williams & Wilkins, Philadelphia, PA, pp. 833-855.Google Scholar
  45. Williams, S. M. and Goldman-Rakic, P. S. (1998) Widespread origin of the primate mesofron-tal dopamine system. Cereb. Cortex. 8, 321-345.CrossRefPubMedGoogle Scholar
  46. Winterer, G. and Weinberger, D. R. (2004) Genes, dopamine and cortical signal-to-noise ratio in schizophrenia. Trends. Neurosci. 27, 683-690.CrossRefPubMedGoogle Scholar
  47. Yamashita, K. and Tanaka, S. (2003) Circuit properties of the cortico-mesocortical system. Neurocomputing. 52-54, 969-975.CrossRefGoogle Scholar
  48. Yamashita, K. and Tanaka, S. (2005) Parametric study of dopaminergic neuromodulatory effects in a reduced model of the prefrontal cortex. Neurocomputing. 65-66, 579-586.CrossRefGoogle Scholar

Copyright information

© Springer Science+Business Media, LLC 2007

Authors and Affiliations

  • Shoji Tanaka
    • 1
  1. 1.Department of Electrical and Electronics EngineeringSophia UniversityChiyoda-kuJapan

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