Unilateral striatal dopamine depletion: time-dependent effects on cortical function and behavioural correlates.
Previously, we showed that unilateral blockade of D1 dopamine receptors in the striatum inhibits immediate-early gene expression bilaterally throughout large parts of the cortex, including sensory-evoked expression in the barrel cortex. To further investigate this dopamine regulation of cortical function, we examined the effects of dopamine depletion on cortical gene regulation and behavioural correlates. Two days after unilateral infusion of 6-hydroxydopamine into the midbrain, rats displayed a (to some degree) bilateral reduction in cortical zif 268 expression that was more pronounced on the lesioned side. This decrease was found across motor, somatosensory, insular and piriform, but not cingulate, cortex, similar to the effects of blockade of striatal D1 receptors. Furthermore, whisker stimulation-evoked c-fos and zif 268 expression in the barrel cortex ipsilateral to the lesion was also attenuated by acute dopamine depletion. These cortical deficits were accompanied by a breakdown of spontaneous behaviours in an open-field test. In contrast, 21 days after dopamine depletion, both basal and sensory-evoked gene expression in the cortex were near-normal. This cortical recovery was paralleled by recovery in locomotion and in sensory-guided behaviour (scanning) related to the hemisphere contralateral to the lesion, but not in scanning by the dopamine-depleted hemisphere. Our results suggest that striatal dopamine exerts a widespread facilitatory influence on cortical function that is necessary, but not sufficient, for normal behaviour. Moreover, the mechanisms mediating this cortical facilitation appear to be subject to substantial neuroplasticity after dopamine perturbation.
Steiner
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Department of Anatomy and Neurobiology, College of Medicine, University of Tennessee, Memphis, TN 38163, USA. steinerh@finchcms.edu
Kitai
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D000818:Animals; D001522:Behavior, Animal / Q000187:drug effects / Q000502:physiology; D004268:DNA-Binding Proteins / Q000235:genetics; D004298:Dopamine / Q000172:deficiency*; D051766:Early Growth Response Protein 1; D004745:Enkephalins / Q000187:drug effects / Q000378:metabolism; D007839:Functional Laterality / Q000502:physiology; D005786:Gene Expression Regulation / Q000187:drug effects / Q000502:physiology*; D017874:Immediate-Early Proteins; D008297:Male; D017072:Neostriatum / Q000187:drug effects / Q000378:metabolism*; D009434:Neural Pathways / Q000187:drug effects / Q000378:metabolism*; D009473:Neuronal Plasticity / Q000187:drug effects / Q000502:physiology; D009474:Neurons / Q000187:drug effects / Q000378:metabolism*; D009714:Nucleus Accumbens / Q000187:drug effects / Q000378:metabolism; D016627:Oxidopamine / Q000494:pharmacology; D016760:Proto-Oncogene Proteins c-fos / Q000235:genetics; D012333:RNA, Messenger / Q000187:drug effects / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D017447:Receptors, Dopamine D1 / Q000187:drug effects / Q000378:metabolism; D013003:Somatosensory Cortex / Q000187:drug effects / Q000378:metabolism*; D013565:Sympatholytics / Q000494:pharmacology; D013997:Time Factors; D014157:Transcription Factors / Q000235:genetics; D014446:Tyrosine 3-Monooxygenase / Q000187:drug effects / Q000378:metabolism; D014738:Vibrissae / Q000502:physiology
D004268:DNA-Binding Proteins; D051766:Early Growth Response Protein 1; C486110:Egr1 protein, rat; D004745:Enkephalins; D017874:Immediate-Early Proteins; D016760:Proto-Oncogene Proteins c-fos; D012333:RNA, Messenger; D017447:Receptors, Dopamine D1; D013565:Sympatholytics; D014157:Transcription Factors; D016627:Oxidopamine; D014446:Tyrosine 3-Monooxygenase; D004298:Dopamine