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Dopamine is Required for Activity-Dependent Amplification of Arc mRNA in Developing Postnatal Frontal Cortex
Yizhou Ye1, Surjeet Mastwal1, Vania Yu Cao1
1Unit on Neural Circuits and Adaptive Behaviors, Clinical and Translational Neuroscience Branch, National Institute of Mental Health, National Institutes of Health, Bethesda, MD 20892, USA.
Cerebral Cortex (New York, N.Y. : 1991)
|July 2, 2016
Summary
Dopamine is essential for amplifying Arc mRNA in the developing frontal cortex. This process requires both electrical stimulation and dopamine D1 receptor activation, crucial for normal gene expression related to schizophrenia.
Area of Science:
- Neuroscience
- Molecular Biology
- Developmental Biology
Background:
- The Arc/Arg3.1 gene encodes a postsynaptic protein vital for synaptic plasticity.
- Altered Arc expression and genetic mutations in the Arc pathway are linked to schizophrenia.
- Arc mRNA levels change with age, but regulatory mechanisms in the developing frontal cortex are unknown.
Purpose of the Study:
- To investigate the mechanisms regulating Arc mRNA levels in the postnatal frontal cortex.
- To determine the role of dopamine and neural activity in Arc gene expression during development.
Main Methods:
- Quantitative mRNA analysis of mouse frontal cortical tissues.
- Investigated Arc mRNA amplification in response to electrical stimulation and dopamine D1 receptor activation.
- Examined the impact of visual stimuli and ventral midbrain dopamine neurons.
Main Results:
- Arc mRNA levels sharply increase in the second postnatal week, coinciding with eye-opening.
- Electrical stimulation alone before eye-opening does not amplify Arc mRNA.
- Arc mRNA amplification requires both electrical stimulation and dopamine D1 receptor activation.
- Visual stimuli-driven Arc mRNA amplification depends on D1 receptor activation and dopamine neurons.
Conclusions:
- Dopamine is required for activity-dependent Arc mRNA amplification in the developing frontal cortex.
- Joint electrical and dopaminergic activation is essential for establishing normal Arc gene expression patterns.
- Findings suggest a mechanism for how dopamine influences the expression of a schizophrenia-associated gene during development.
