• Neuroscience · Aug 2020

    Post-pubertal difference in nigral dopaminergic cells firing in the schizophrenia model prepared by perinatal challenges of a cytokine, EGF.

    • Hisaaki Namba and Hiroyuki Nawa.
    • Department of Molecular Neurobiology, Brain Research Institute, Niigata University, Niigata 951-8585, Japan. Electronic address: hnamba@bri.niigata-u.ac.jp.
    • Neuroscience. 2020 Aug 10; 441: 22-32.

    AbstractSchizophrenia in humans typically develops during and after adolescence; however, the biological underpinning for the specificity of this onset time window remains to be determined. In the present study, we investigated this knowledge gap using our own animal model for schizophrenia. Rodents and monkeys challenged with a cytokine, epidermal growth factor (EGF), as neonates are known to exhibit various behavioral and cognitive abnormalities at the post-pubertal stage. We used the EGF-challenged mice as an animal model for schizophrenia to evaluate the electrophysiological impact of this modeling on nigral dopamine neurons before and after puberty. In vivo single unit recording revealed that the burst firing of putative dopamine neurons in substantia nigra pars compacta was significantly higher in the post-pubertal stage of the EGF model than in that of control mice; in contrast, this difference was not observed in the pre-pubertal stage. The increase in burst firing was accompanied by a decline in Ca2+-activated K+ (ISK) currents, which influence the firing pattern of dopamine neurons. In vivo local application of the SK channel blocker apamin (80 μM) to the substantia nigra was less effective at increasing burst firing in the EGF model than in control mice, suggesting the pathologic role of the ISK decrease in this model. Thus, these results suggest that the aberrant post-pubertal hyperactivity of midbrain dopaminergic neurons is associated with the temporal specificity of the behavioral deficit of this model, and support the hypothesis that this dopaminergic aberration could be implicated in the adolescent onset of schizophrenia.Copyright © 2020 IBRO. Published by Elsevier Ltd. All rights reserved.

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