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Prefrontal Cortical Synaptic Plasticity: The Roles of Dopamine and Implication for Schizophrenia

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Monoaminergic Modulation of Cortical Excitability

The prefrontal cortex (PFC) is central in mediating executive functions in goaldirected behavior, for which proper dopamine (DA) actions of information processing modulation is essential in this area. It is now evident that, as in the case of the hippocampus, the PFC undergoes neuronal adaptation processes in its networks with induction of synaptic plasticity such as long-term potentiation (LTP) and short-term potentiation (STP). A prominent characteristic of synaptic plasticity in the PFC is that its induction mechanisms involve DA as an essential modulatory molecule. As such, DA-dependent plastic changes occurring in PFC network have important roles for PFC-mediated cognitive functions. Nevertheless, little attempt has been made to characterize the nature of PFC neuronal adaptation by synaptic plasticity, given that the PFC is thought to be the area of temporary storage and manipulation of information, known as working memory. However, accumulating evidences now indicate that the functions of the PFC cannot be fully explained just as the region of an online representation and handling of information. Importance of DA-dependent synaptic plasticity is further encouraged by possible disruption of synaptic plasticity mechanism in the PFC in psychiatric disorders such as schizophrenia, drug addiction, and depression.

In this chapter, we describe the underlying cellular mechanisms of DA action on synaptic plasticity induction in the PFC, and possible roles of PFC synaptic plasticity in executive functions as well as its disruptions in the pathophysiology of schizophrenia.

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References

  • Abi-Dargham, A., Mawlawi, O., Lombardo, I., Gil, R., Martinez, D., Huang, Y., Hwang, D. R., Keilp, J., Kochan, L., Van Heertum, R., Gorman, J. M., and Laruelle, M. (2002). Pre-frontal dopamine D1 receptors and working memory in schizophrenia. J Neurosci 22, 3708-19.

    PubMed  CAS  Google Scholar 

  • Au-Young, S. M., Shen, H., and Yang, C. R. (1999). Medial prefrontal cortical output neurons to the ventral tegmental area (VTA) and their responses to burst-patterned stimulation of the VTA: neuroanatomical and in vivo electrophysiological analyses. Synapse 34, 245-55.

    Article  PubMed  CAS  Google Scholar 

  • Baldwin, A. E., Sadeghian, K., and Kelley, A. E. (2002). Appetitive instrumental learning requires coincident activation of NMDA and dopamine D1 receptors within the medial prefrontal cortex. J Neurosci 22, 1063-71.

    PubMed  CAS  Google Scholar 

  • Bear, M. F., and Malenka, R. C. (1994). Synaptic plasticity: LTP and LTD. Curr Opin Neuro-biol 4, 389-99.

    Article  CAS  Google Scholar 

  • Benes, F. M. (1999). Evidence for altered trisynaptic circuitry in schizophrenic hippocampus. Biol Psychiatry 46, 589-99.

    Article  PubMed  CAS  Google Scholar 

  • Birrell, J. M., and Brown, V. J. (2000). Medial frontal cortex mediates perceptual attentional set shifting in the rat. J Neurosci 20, 4320-4.

    PubMed  CAS  Google Scholar 

  • 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, 2209-15.

    Article  PubMed  Google Scholar 

  • Carr, D. B., and Sesack, S. R. (2000). Projections from the rat prefrontal cortex to the ventral tegmental area: target specificity in the synaptic associations with mesoaccumbens and mesocortical neurons. J Neurosci 20, 3864-73.

    PubMed  CAS  Google Scholar 

  • Egerton, A., Reid, L., McKerchar, C. E., Morris, B. J., and Pratt, J. A. (2005). Impairment in perceptual attentional set-shifting following PCP administration: a rodent model of set-shifting deficits in schizophrenia. Psychopharmacology (Berl) 179, 77-84.

    Article  CAS  Google Scholar 

  • Fuster, J. M., Bodner, M., and Kroger, J. K. (2000). Cross-modal and cross-temporal associa-tion in neurons of frontal cortex. Nature 405, 347-51.

    Article  PubMed  CAS  Google Scholar 

  • Goldman-Rakic, P. S. (1995). Cellular basis of working memory. Neuron 14, 477-85.

    Article  PubMed  CAS  Google Scholar 

  • Goldman-Rakic, P. S., and Selemon, L. D. (1997). Functional and anatomical aspects of pre-frontal pathology in schizophrenia. Schizophr Bull 23, 437-58.

    PubMed  CAS  Google Scholar 

  • Gorelova, N., Seamans, J. K., and Yang, C. R. (2002). Mechanisms of dopamine activation of fast-spiking interneurons that exert inhibition in rat prefrontal cortex. J Neurophysiol 88, 3150-66.

    Article  PubMed  CAS  Google Scholar 

  • Goto, Y., and Grace, A. A. (2006). Alterations in medial prefrontal cortical activity and plas-ticity in rats with disruption of cortical development. Biol Psychiatry, 60, 1259-67.

    Article  PubMed  Google Scholar 

  • Greengard, P., Allen, P. B., and Nairn, A. C. (1999). Beyond the dopamine receptor: the DARPP-32/protein phosphatase-1 cascade. Neuron 23, 435-47.

    Article  PubMed  CAS  Google Scholar 

  • Gurden, H., Takita, M., and Jay, T. M. (2000). Essential role of D1 but not D2 receptors in the NMDA receptor-dependent long-term potentiation at hippocampal-prefrontal cortex syn-apses in vivo. J Neurosci 20, RC106.

    PubMed  CAS  Google Scholar 

  • Gurden, H., Tassin, J.-P., and Jay, T. M. (1999). Integrity of the mesocortical dopaminergic system is necessary for complete expression of in vivo hippocampal-prefrontal cortex long-term potentiation. Neuroscience 94, 1019-27.

    Article  PubMed  CAS  Google Scholar 

  • Harrison, P. J., and Weinberger, D. R. (2005). Schizophrenia genes, gene expression, and neuropathology: on the matter of their convergence. Mol Psychiatry 10, 40-68.

    Article  PubMed  CAS  Google Scholar 

  • Haut, M. W., Cahill, J., Cutlip, W. D., Stevenson, J. M., Makela, E. H., and Bloomfield, S. M. (1996). On the nature of Wisconsin Card Sorting Test performance in schizophrenia. Psy-chiatry Res 65, 15-22.

    Article  CAS  Google Scholar 

  • Heckers, S., Rauch, S. L., Goff, D., Savage, C. R., Schacter, D. L., Fischman, A. J., and Alpert, N. M. (1998). Impaired recruitment of the hippocampus during conscious recollec-tion in schizophrenia. Nat Neurosci 1, 318-23.

    Article  PubMed  CAS  Google Scholar 

  • Herry, C., and Garcia, R. (2002). Prefrontal cortex long-term potentiation, but not long-term depression, is associated with the maintenance of extinction of learned fear in mice. J Neurosci 22, 577-83.

    PubMed  CAS  Google Scholar 

  • Huang, Y. Y., Simpson, E., Kellendonk, C., and Kandel, E. R. (2004). Genetic evidence for the bidirectional modulation of synaptic plasticity in the prefrontal cortex by D1 receptors. Proc Natl Acad Sci U S A 101, 3236-41.

    Article  PubMed  CAS  Google Scholar 

  • Javitt, D. C., and Zukin, S. R. (1991). Recent advances in the phencyclidine model of schizo-phrenia. Am J Psychiatry 148, 1301-8.

    PubMed  CAS  Google Scholar 

  • Jay, T. M., and Witter, M. P. (1991). Distribution of hippocampal CA1 and subicular efferents in the prefrontal cortex of the rat studied by means of anterograde transport of Phaseolus vulgaris-leucoagglutinin. J Comp Neurol 313, 574-86.

    Article  PubMed  CAS  Google Scholar 

  • Jentsch, J. D., and Roth, R. H. (1999). The neuropsychopharmacology of phencyclidine: from NMDA receptor hypofunction to the dopamine hypothesis of schizophrenia. Neuropsy-chopharmacology 20, 201-25.

    Article  CAS  Google Scholar 

  • Klemm, W. R. (1976). Physiological and behavioral significance of hippocampal rhythmic, slow activity (“theta rhythm”). Prog Neurobiol 6, 23-47.

    Article  PubMed  CAS  Google Scholar 

  • Knable, M. B., and Weinberger, D. R. (1997). Dopamine, the prefrontal cortex and schizo-phrenia. J Psychopharmacol 11, 123-31.

    Article  PubMed  CAS  Google Scholar 

  • Laruelle, M., Kegeles, L. S., and Abi-Dargham, A. (2003). Glutamate, dopamine, and schizo-phrenia: from pathophysiology to treatment. Ann N Y Acad Sci 1003, 138-58.

    Article  PubMed  CAS  Google Scholar 

  • Levitt, J. B., Lewis, D. A., Yoshioka, T., and Lund, J. S. (1993). Topography of pyramidal neuron intrinsic connections in macaque monkey prefrontal cortex (areas 9 and 46). J Comp Neurol 338, 360-76.

    Article  PubMed  CAS  Google Scholar 

  • Lewis, D. A., Campbell, M. J., Foote, S. L., Goldstein, M., and Morrison, J. H. (1987). The distribution of tyrosine hydroxylase-immunoreactive fibers in primate neocortex is wide-spread but regionally specific. J Neurosci 7, 279-90.

    PubMed  CAS  Google Scholar 

  • Lidow, M. S., Goldman-Rakic, P. S., Gallager, D. W., and Rakic, P. (1991). Distribution of dopaminergic receptors in the primate cerebral cortex: quantitative audioradiographic analysis using [3H]raclopride, [3H]spiperone, and [3H]SCH23390. Neuroscience 40, 657-71.

    Article  PubMed  CAS  Google Scholar 

  • Lidow, M. S., Williams, G. V., and Goldman-Rakic, P. S. (1998). The cerebral cortex: a case for a common site of action of antipsychotics. Trends Pharmacol Sci 19, 136-40.

    Article  PubMed  CAS  Google Scholar 

  • Manoach, D. S. (2003). Prefrontal cortex dysfunction during working memory performance in schizophrenia: reconciling discrepant findings. Schizophr Res 60, 285-98.

    Article  PubMed  Google Scholar 

  • Matsuda, Y., Marzo, A., and Otani, S. (2006). The presence of background dopamine signal converts long-term synaptic depression to potentiation in rat prefrontal cortex. J Neurosci 26, 4803-10.

    Article  PubMed  CAS  Google Scholar 

  • Meyer-Lindenberg, A. S., Olsen, R. K., Kohn, P. D., Brown, T., Egan, M. F., Weinberger, D. R., and Berman, K. F. (2005). Regionally specific disturbance of dorsolateral prefrontal-hippocampal functional connectivity in schizophrenia. Arch Gen Psychiatry 62, 379-86.

    Article  PubMed  Google Scholar 

  • Miller, E. K., and Cohen, J. D. (2001). An integrative theory of prefrontal cortex function. Annu Rev Neurosci 24, 167-202.

    Article  PubMed  CAS  Google Scholar 

  • Mulder, A. B., Nordquist, R., Orgut, O., and Pennartz, C. M. (2000). Plasticity of neuronal firing in deep layers of the medial prefrontal cortex in rats engaged in operant condition-ing. Prog Brain Res 126, 287-301.

    Article  PubMed  CAS  Google Scholar 

  • Murase, S., Grenhoff, J., Chouvet, G., Gonon, F. G., and Svensson, T. H. (1993). Prefrontal cortex regulates burst firing and transmitter release in rat mesolimbic dopamine neurons studied in vivo. Neurosci Lett 157, 53-6.

    Article  PubMed  CAS  Google Scholar 

  • 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 pre-frontal dopamine D1 receptors in schizophrenia revealed by PET. Nature 385, 634-6.

    Article  PubMed  CAS  Google Scholar 

  • Otani, S., Auclair, N., Desce, J.-M., Roisin, M.-P., and Crepel, F. (1999). Dopamine receptors and groups I and II mGluRs cooperate for long-term depression induction in rat pre-frontal cortex through converging postsynaptic activation of MAP kinases. J Neurosci 19, 9788-02.

    PubMed  CAS  Google Scholar 

  • Otani, S., Blond, O., Desce, J. M., and Crepel, F. (1998). Dopamine facilitates long-term depression of glutamatergic transmission in rat prefrontal cortex. Neuroscience 85, 669-76.

    Article  PubMed  CAS  Google Scholar 

  • Runyan, J. D., Moore, A. N., and Dash, P. K. (2004). A role for prefrontal cortex in memory storage for trace fear conditioning. J Neurosci 24, 1288-95.

    Article  PubMed  CAS  Google Scholar 

  • Seamans, J. K., Durstewitz, D., Christie, B. R., Stevens, C. F., and Sejnowski, T. J. (2001). Dopamine D1/D5 receptor modulation of excitatory synaptic inputs to layer V prefrontal cortex neurons. Proc Natl Acad Sci U S A 98, 301-6.

    Article  PubMed  CAS  Google Scholar 

  • Simon, B., Knuckley, B., Churchwell, J., and Powell, D. A. (2005). Post-training lesions of the medial prefrontal cortex interfere with subsequent performance of trace eyeblink condi-tioning. J Neurosci 25, 10740-6.

    Article  PubMed  CAS  Google Scholar 

  • Takehara-Nishiuchi, K., Nakao, K., Kawahara, S., Matsuki, N., and Kirino, Y. (2006). Sys-tems consolidation requires postlearning activation of NMDA receptors in the medial pre-frontal cortex in trace eyeblink conditioning. J Neurosci 26, 5049-58.

    Article  PubMed  CAS  Google Scholar 

  • Takita, M., Izaki, Y., Jay, T. M., Kaneko, H., and Suzuki, S. S. (1999). Induction of stable long-term depression in vivo in the hippocampal-prefrontal cortex pathway. Eur J Neuro-sci 11, 4145-8.

    Article  CAS  Google Scholar 

  • Tallon-Baudry, C., Bertrand, O., Peronnet, F., and Pernier, J. (1998). Induced gamma-band activity during the delay of a visual short-term memory task in humans. J Neurosci 18, 4244-54.

    PubMed  CAS  Google Scholar 

  • Thierry, A. M., Blanc, G., Sobel, A., Stinus, L., and Golwinski, J. (1973). Dopaminergic terminals in the rat cortex. Science 182, 499-501.

    Article  PubMed  CAS  Google Scholar 

  • Trantham-Davidson, H., Neely, L. C., Lavin, A., and Seamans, J. K. (2004). Mechanisms underlying differential D1 versus D2 dopamine receptor regulation of inhibition in pre-frontal cortex. J Neurosci 24, 10652-9.

    Article  PubMed  CAS  Google Scholar 

  • Tseng, K. Y., and O’Donnell, P. (2004). Dopamine-glutamate interactions controlling prefron-tal cortical pyramidal cell excitability involve multiple signaling mechanisms. J Neurosci 24, 5131-9.

    Article  PubMed  CAS  Google Scholar 

  • Tseng, K. Y., and O’Donnell, P. (2007). Dopamine modulation of prefrontal cortical interneu-rons changes during adolescence. Cereb Cortex 17, 1235-40.

    Article  PubMed  Google Scholar 

  • Wallis, J. D., Anderson, K. C., and Miller, E. K. (2001). Single neurons in prefrontal cortex encode abstract rules. Nature 411, 953-6.

    Article  PubMed  CAS  Google Scholar 

  • Wang, Y., and Goldman-Rakic, P. S. (2004). D2 receptor regulation of synaptic burst firing in prefrontal cortical pyramidal neurons. Proc Natl Acad Sci U S A 101, 5093-8.

    Article  PubMed  CAS  Google Scholar 

  • Weinberger, D. R., Aloia, M. S., Goldberg, T. E., and Berman, K. F. (1994). The frontal lobes and schizophrenia. J Neuropsychiatry Clin Neurosci 6, 419-27.

    PubMed  CAS  Google Scholar 

  • Weiner, D. M., Levey, A. I., Sunahara, R. K., Niznik, H. B., O’Dowd, B. F., Seeman, P., and Brann, M. R. (1991). D1 and D2 dopamine receptor mRNA in rat brain. Proc Natl Acad Sci U S A 88, 1859-63.

    Article  PubMed  CAS  Google Scholar 

  • Williams, G. V., and Castner, S. A. (2006). Under the curve: critical issues for elucidating D1 receptor function in working memory. Neuroscience 139, 263-76.

    Article  PubMed  CAS  Google Scholar 

  • Yang, C. R., and Chen, L. (2005). Targeting prefrontal cortical dopamine D1 and N-methyl-D-aspartate receptor interactions in schizophrenia treatment. Neuroscientist 11, 452-70.

    Article  PubMed  CAS  Google Scholar 

  • Yang, C. R., and Seamans, J. K. (1996). Dopamine D1 receptor actions in layers V-VI rat prefrontal cortex neurons in vitro: modulation of dendritic-somatic signal integration. J Neurosci 16, 1922-35.

    PubMed  CAS  Google Scholar 

  • Yerkes, R. M., and Dodson, J. D. (1908). The relation of strength of stimulus to rapidity of habit-formation. J Comp Neurol Psychol 18, 459-82.

    Article  Google Scholar 

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Goto, Y., Otani, S. (2007). Prefrontal Cortical Synaptic Plasticity: The Roles of Dopamine and Implication for Schizophrenia. In: Tseng, KY., Atzori, M. (eds) Monoaminergic Modulation of Cortical Excitability. Springer, Boston, MA. https://doi.org/10.1007/978-0-387-72256-6_10

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