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Altered neurocircuitry in the dopamine transporter knockout mouse brain
Xiaowei Zhang1, Elaine L Bearer, Benoit Boulat
1Biological Imaging Center, Beckman Institute, California Institute of Technology, Pasadena, California, United States of America.
Plos One
|July 17, 2010
Summary
Dopamine transporter knockout mice show normal brain structure but altered reward circuitry. Manganese-enhanced MRI reveals diminished connectivity in dopamine transporter (DAT) knockout mice, impacting reward pathways beyond the thalamus.
Area of Science:
- Neuroscience
- Neuroimaging
- Genetics
Background:
- Plasma membrane transporters for monoamine neurotransmitters like dopamine are crucial for brain function and neurological disorders.
- Gene knockout (KO) models, including dopamine transporter (DAT) KO mice, offer insights into transporter function at molecular, physiological, and behavioral levels.
- Magnetic resonance imaging (MRI) can probe brain morphology and circuitry affected by altered neurotransmitter dynamics.
Purpose of the Study:
- To investigate the effects of altered dopaminergic dynamics on meso-scale neuronal circuitry and brain morphology in DAT KO mice using MRI.
- To identify morphological or metabolic changes in DAT KO mice that could explain observed behavioral and pharmacological differences.
- To assess the functional connectivity of reward pathways in DAT KO mice.
Main Methods:
- High-resolution structural MRI was used for voxel-wise statistical comparison of brain morphology between DAT KO and wild-type (WT) mice.
- Proton magnetic resonance spectroscopy was employed to analyze metabolite concentrations in the striatum.
- Manganese-enhanced MRI (MEMRI) was utilized to visualize neuronal circuitry alterations following manganese ion (Mn(2+)) injection into the prefrontal cortex.
Main Results:
- Structural MRI revealed minimal morphological changes in DAT KO mice compared to WT.
- Proton magnetic resonance spectroscopy showed no significant differences in detectable striatal metabolite concentrations.
- MEMRI demonstrated a truncated Mn(2+) distribution in DAT KO mice, with limited accumulation beyond the thalamus, indicating diminished reward circuitry robustness distal to the thalamus.
Conclusions:
- DAT KO mice exhibit preserved cortico-striatal-thalamic connectivity but show reduced robustness in reward-modulating circuitry.
- These findings suggest that DAT KO impacts specific downstream reward pathways, contrasting with observations in serotonin transporter KO mice.
- MRI techniques, particularly MEMRI, are effective in revealing functional circuitry alterations in genetically modified mouse models.
