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Altered reward circuitry in the norepinephrine transporter knockout mouse
Joseph J Gallagher1, Xiaowei Zhang, F Scott Hall
1Biological Imaging Center, Beckman Institute, California Institute of Technology, Pasadena, California, United States of America.
Plos One
|March 8, 2013
Summary
Genetic deletion of the norepinephrine transporter (NET) in mice alters brain reward circuitry, showing anterior bias in functional connectivity, similar to dopamine transporter (DAT) knockouts but unlike serotonin transporter (SERT) knockouts.
Area of Science:
- Neuroscience
- Molecular Biology
- Genetics
Background:
- Monoamine neurotransmitters (dopamine, serotonin, norepinephrine) regulate synaptic signaling.
- Plasma membrane transporters modulate neurotransmitter levels, influencing neurological and psychiatric disorders.
- Norepinephrine transporter (NET) plays a key role in norepinephrine signaling.
Purpose of the Study:
- Investigate the effects of genetic norepinephrine transporter deletion on brain metabolism, anatomy, and functional connectivity.
- Utilize in vivo magnetic resonance imaging and histological analyses.
- Compare NET knockout mice to dopamine transporter (DAT) and serotonin transporter (SERT) knockout models.
Main Methods:
- In vivo magnetic resonance spectroscopy (MRS) and imaging.
- Tensor-based morphometric analysis.
- Manganese-enhanced MRI (MEMRI) for neuronal circuitry tracing.
- Histological examination.
Main Results:
- NET knockout mice showed reduced NAA in the striatum, correlating with minor dysmorphisms.
- Structural analysis revealed minimal anatomical alterations.
- MEMRI indicated an anterior bias in the reward circuit's functional connectivity.
- NET knockout mice exhibited antidepressant-like behaviors.
Conclusions:
- Genetic deletion of NET impacts brain metabolism and functional connectivity, particularly in the reward circuit.
- The anterior bias in connectivity observed in NET knockout mice resembles DAT knockout mice.
- Findings suggest distinct roles for NET, DAT, and SERT in brain circuitry and behavior.
