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Neonatal lesions of the medial temporal lobe disrupt prefrontal cortical regulation of striatal dopamine

Abstract

The effects of early brain damage are often, but not always, milder than the effects of comparable damage in adults, depending on the age at which injury occurred, the region of the brain damaged, and the brain functions involved1,2,3,4,5,6,7. Studies of the impact of early brain damage have generally focused on functions primarily associated with the neural structures injured, even though the development and function of distant but interconnected neural systems might also show effects. Here we examine the regulation of striatal dopamine by the dorsolateral prefrontal cortex, in adult monkeys that had had either neonatal or adult lesions of themedial–temporal lobe and in normal animals. We use microdialysis to measure the dopamine response in the caudate nucleus after the infusion of amphetamine into the dorsolateral prefrontal cortex. Normal animals and those with adult lesions showed a reduction in dopamine overflow; in contrast, monkeys with neonatal lesions showed increased dopamine release. Thus, early injury to the primate medial–temporal lobe disrupts the normal regulation of striatal dopamine activity by the dorsolateral prefrontal cortex during adulthood. Early focal lesions may have substantial and long-lasting impacts on the function of a distant neural system.

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Figure 1: Magnetic resonance images of monkeys, showing rostral-to-caudal coronal sections.
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References

  1. Goldman-Rakic, P. S., Isseroff, A., Schwartz, M. L. & Bugbee, N. M. in Handbook of Cognitive Development: Biology and Infancy Development (ed. Mussen, P.) 281–344 (John Wiley, New York, 1983).

    Google Scholar 

  2. Kolb, B. Recovery from early cortical damage in rats: I. Differential behavioral and anatomical effects of frontal lesions at 1 or 5 days of age. Behav. Brain Res. 25, 205–220 (1987).

    Article  CAS  Google Scholar 

  3. Goldman, P. S. in Plasticity and Recovery from Brain Damage (eds Stein, D. G., Rosen, J. J. & Butters,N.) 149–174 (Academic, New York, 1974).

    Google Scholar 

  4. Malkova, L., Mishkin, M. & Bachevalier, J. Long-term effects of selective neonatal temporal lobe lesions on learning and memory in monkeys. Behav. Neurosci. 109, 212–226 (1995).

    Article  CAS  Google Scholar 

  5. Mahut, M. & Moss, M. in The HippocampusVol. 4 (eds Isaacson, R. L. & Pribram, K. H.) 241–279 (Plenum, New York, 1986).

    Book  Google Scholar 

  6. Lipska, B. K. & Weinberger, D. R. Genetic variation in vulnerability to the behavioral effects of neonatal hippocampal damage in rats. Proc. Natl Acad. Sci. USA 92, 8906–8910 (1995).

    Article  ADS  CAS  Google Scholar 

  7. Malkova, L., Mishkin, M., Suomi, S. J. & Bachevalier, J. Socioemotional behavior in adult rhesus monkeys after early versus late lesions of the medial temporal lobe. Ann. NY Acad. Sci. 807, 538–540 (1997).

    Article  ADS  CAS  Google Scholar 

  8. Fuster, J. M. The Prefrontal Cortex: Anatomy, Physiology, and Neuropsychology of the Frontal Lobe (Raven, New York, 1989).

    Google Scholar 

  9. Roberts, A. C.et al. 6-Hydroxydopamine lesions of the prefrontal cortex in monkeys enhance performance on an analog of the Wisconsin card sort test: possible interaction with subcortical dopamine. J. Neurosci. 14, 2531–2544 (1994).

    Article  CAS  Google Scholar 

  10. Kolachana, B. S., Saunders, R. C. & Weinberger, D. R. Augmentation of prefrontal cortical monoaminergic activity inhibits dopamine release in the caudate nucleus: an in vivo neurochemical assessment in the rhesus monkey. Neuroscience 69, 859–868 (1995).

    Article  CAS  Google Scholar 

  11. Moghaddam, B., Berridge, C. W., Goldman-Rakic, P. S., Bunney, B. S. & Roth, R. H. In vivo assessment of basal and drug-induced dopamine release in cortical and subcortical regions of the anesthetized primate. Synapse 13, 215–222 (1993).

    Article  CAS  Google Scholar 

  12. Sesack, S. R. & Pickel, V. M. Prefrontal cortical efferents in the rat synapse on unlabeled neuronal targets of catecholamine terminals in the nucleus accumbens septi and on dopamine neurons in the ventral tegmental area. J. Comp. Neurol. 320, 145–160 (1992).

    Article  CAS  Google Scholar 

  13. Taber, M. T., Das, S. & Fibiger, H. C. Cortical regulation of subcortical dopamine release: mediation via the ventral tegmental area. J. Neurochem. 65, 1407–1410 (1995).

    Article  CAS  Google Scholar 

  14. Karreman, M. & Moghaddam, B. The prefrontal cortex regulates the basal release of dopamine in the limbic striatum: an effect mediated by ventral tegmental area. J. Neurochem. 66, 589–598 (1996).

    Article  CAS  Google Scholar 

  15. Kolb, B., Gibb, R. & van der Kooy, D. Neonatal frontal cortical lesions in rats alter cortical structure and connectivity. Brain Res. 645, 85–97 (1994).

    Article  CAS  Google Scholar 

  16. Webster, M. J., Ungerleider, L. G. & Bachevalier, J. Lesions of inferior temporal area TE in infant monkeys alter cortico-amygdalar projections. Neuroreport 2, 769–772 (1991).

    Article  CAS  Google Scholar 

  17. Goldman-Rakic, P. S., Selemon, L. D. & Schwartz, M. L. Dual pathways connecting the dorsolateral prefrontal cortex with the hippocampal formation and parahippocampal cortex in the rhesus monkey. Neuroscience 12, 719–743 (1984).

    Article  CAS  Google Scholar 

  18. Russchen, F. T., Bakst, I., Amaral, D. G. & Price, J. L. The amygdaloid projections in the monkey. An anterograde tracing study. Brain Res. 329, 241–257 (1985).

    Article  CAS  Google Scholar 

  19. Smith, Y. & Parent, A. Differential connections of caudate nucleus and putamen in the squirrel monkey (Saimiri sciurens). Neuroscience 18, 347–371 (1986).

    Article  ADS  CAS  Google Scholar 

  20. Hikosaka, O., Sakamoto, M. & Miyashita, N. Effects of caudate nucleus stimulation on substantia nigra cell activity in monkey. Exp. Brain Res. 95, 457–472 (1993).

    Article  CAS  Google Scholar 

  21. Bertolino, A.et al. Altered development of prefrontal neurons in rhesus monkeys with neonatal mesial temporo-limbic lesions: a proton magnetic resonance spectroscopic imaging study. Cerebral Cortex 7, 740–748 (1997).

    Article  CAS  Google Scholar 

  22. Jakob, H. & Beckman, H. Prenatal developmental disturbances in the limbic allocortex in schizophrenics. J. Neural Trans. 65, 303–326 (1986).

    Article  CAS  Google Scholar 

  23. Weinberger, D. R. & Berman, K. F. Prefrontal function in schizophrenia: confounds and controversies. Phil. Trans. R. Soc. Lond. B 351, 1495–1503 (1996).

    Article  CAS  Google Scholar 

  24. Carlson, A., Hansson, L. O., Waters, N. & Carlsson, M. L. Neurotransmitter aberration in schizophrenia: new perspectives and therapeutic implications. Life Sci. 61, 75–94 (1997).

    Article  Google Scholar 

  25. Weinberger, D. R. & Lipska, B. K. Cortical maldevelopment, anti-psychotic drugs, and schizophrenia: a search for common ground. Schizophrenia Res. 16, 87–110 (1995).

    Article  CAS  Google Scholar 

  26. Bebbington, P. E., Bowen, J., Hirsch, S. R. & Kuipers, E. A. in Schizophrenia (eds Hirsch, S. R. & Weinberger, D. R.) 587–604 (Blackwell, Oxford, 1995).

    Google Scholar 

  27. Breier, A.et al. Schizophrenia is associated with elevated amphetamine-induced synaptic dopamine concentrations: evidence from a novel positron emission method. Proc. Natl Acad. Sci. USA 94, 2569–2574 (1997).

    Article  ADS  CAS  Google Scholar 

  28. Laruelle, M.et al. Single photon emission computerized tomography imaging of amphetamine-induced dopamine release in drug-free schizophrenic subjects. Proc. Natl Acad. Sci. USA 93, 9235–9240 (1997).

    Article  ADS  Google Scholar 

  29. Kolachana, B. S., Saunders, R. C. & Weinberger, D. R. In vivo characterization of extracellular GABA release in the caudate nucleus and prefrontal cortex of the rhesus monkey. Synapse 25, 285–292 (1997).

    Article  CAS  Google Scholar 

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Acknowledgements

We thank J. Gray for technical assistance and B. Lipska for comments on the manuscript. All procedures were carried out in strict adherence to the NIH Guide for the Care and Use of Laboratory Animals.

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Correspondence to Richard C. Saunders.

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Saunders, R., Kolachana, B., Bachevalier, J. et al. Neonatal lesions of the medial temporal lobe disrupt prefrontal cortical regulation of striatal dopamine. Nature 393, 169–171 (1998). https://doi.org/10.1038/30245

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