title: Dopamine is Required for Activity-Dependent Amplification of Arc mRNA in Developing Postnatal Frontal Cortex.
abstract: The activity-regulated gene Arc/Arg3.1 encodes a postsynaptic protein crucially involved in glutamatergic synaptic plasticity. Genetic mutations in Arc pathway and altered Arc expression in human frontal cortex have been associated with schizophrenia. Although Arc expression has been reported to vary with age, what mechanisms regulate Arc mRNA levels in frontal cortex during postnatal development remains unclear. Using quantitative mRNA analysis of mouse frontal cortical tissues, we mapped the developmental profiles of Arc expression and found that its mRNA levels are sharply amplified near the end of the second postnatal week, when mouse pups open their eyes for the first time after birth. Surprisingly, electrical stimulation of the frontal cortex before eye-opening is not sufficient to drive the amplification of Arc mRNA. Instead, this amplification needs both electrical stimulation and dopamine D1-type receptor (D1R) activation. Furthermore, visual stimuli-driven amplification of Arc mRNA is also dependent on D1R activation and dopamine neurons located in the ventral midbrain. These results indicate that dopamine is required to drive activity-dependent amplification of Arc mRNA in the developing postnatal frontal cortex and suggest that joint electrical and dopaminergic activation is essential to establish the normal expression pattern of a schizophrenia-associated gene during frontal cortical development.
authors.affiliation: Unit on Neural Circuits and Adaptive Behaviors, Clinical and Translational Neuroscience Branch, National Institute of Mental Health, National Institutes of Health, Bethesda, MD 20892, USA.
authors.forename: Yizhou
authors.initials: Y
authors.lastname: Ye
authors.affiliation: Unit on Neural Circuits and Adaptive Behaviors, Clinical and Translational Neuroscience Branch, National Institute of Mental Health, National Institutes of Health, Bethesda, MD 20892, USA.
authors.forename: Surjeet
authors.initials: S
authors.lastname: Mastwal
authors.affiliation: Unit on Neural Circuits and Adaptive Behaviors, Clinical and Translational Neuroscience Branch, National Institute of Mental Health, National Institutes of Health, Bethesda, MD 20892, USA.
authors.forename: Vania Yu
authors.initials: VY
authors.lastname: Cao
authors.affiliation: Unit on Neural Circuits and Adaptive Behaviors, Clinical and Translational Neuroscience Branch, National Institute of Mental Health, National Institutes of Health, Bethesda, MD 20892, USA.
authors.forename: Ming
authors.initials: M
authors.lastname: Ren
authors.affiliation: Unit on Neural Circuits and Adaptive Behaviors, Clinical and Translational Neuroscience Branch, National Institute of Mental Health, National Institutes of Health, Bethesda, MD 20892, USA.
authors.forename: Qing
authors.initials: Q
authors.lastname: Liu
authors.affiliation: Unit on Neural Circuits and Adaptive Behaviors, Clinical and Translational Neuroscience Branch, National Institute of Mental Health, National Institutes of Health, Bethesda, MD 20892, USA.
authors.forename: Wenyu
authors.initials: W
authors.lastname: Zhang
authors.affiliation: Cancer Genetics Branch, National Human Genome Research Institute, National Institutes of Health, Bethesda, MD 20892, USA.
authors.forename: Abdel G
authors.initials: AG
authors.lastname: Elkahloun
authors.affiliation: Unit on Neural Circuits and Adaptive Behaviors, Clinical and Translational Neuroscience Branch, National Institute of Mental Health, National Institutes of Health, Bethesda, MD 20892, USA.
authors.forename: Kuan Hong
authors.initials: KH
authors.lastname: Wang
mesh_terms: D000386:AIDS-Related Complex / Q000235:genetics* / Q000378:metabolism; D018663:Adrenergic Agents / Q000494:pharmacology; D000367:Age Factors; D000661:Amphetamine / Q000494:pharmacology; D000818:Animals; D000831:Animals, Newborn; D000975:Antioxidants / Q000494:pharmacology; D001205:Ascorbic Acid / Q000494:pharmacology; D001552:Benzazepines / Q000494:pharmacology; D004298:Dopamine / Q000378:metabolism*; D015259:Dopamine Agents / Q000494:pharmacology; D059290:Dopaminergic Neurons / Q000187:drug effects; D004597:Electroshock / Q000379:methods; D005625:Frontal Lobe / Q000254:growth & development* / Q000378:metabolism*; D018507:Gene Expression Regulation, Developmental / Q000502:physiology*; D051379:Mice; D008810:Mice, Inbred C57BL; D046228:Microarray Analysis; D016627:Oxidopamine / Q000494:pharmacology; D012333:RNA, Messenger / Q000378:metabolism*; D017447:Receptors, Dopamine D1 / Q000378:metabolism; D017557:Ventral Tegmental Area / Q000166:cytology
chemical_list: D018663:Adrenergic Agents; D000975:Antioxidants; D001552:Benzazepines; D015259:Dopamine Agents; D012333:RNA, Messenger; D017447:Receptors, Dopamine D1; C534628:SCH 23390; D016627:Oxidopamine; D000661:Amphetamine; D001205:Ascorbic Acid; D004298:Dopamine
keywords: activity-dependent gene expression; arc; dopamine; frontal cortex; postnatal development