Localized disruption of Narp in medial prefrontal cortex blocks reinforcer devaluation performance
- Alexander W. Johnson1,2,6,
- Sungho Han3,
- Ashley M. Blouin3,
- Jasjit Saini4,
- Paul F. Worley4,
- Matthew J. During5,
- Peter C. Holland1,4,
- Jay M. Baraban3,4 and
- Irving M. Reti3,4
- 1Department of Psychological and Brain Sciences, Johns Hopkins University, Baltimore, Maryland 21218, USA
- 2Neurogenetics and Behavior Center, Johns Hopkins University, Baltimore, Maryland 21218, USA
- 3Department of Psychiatry and Behavioral Sciences, Johns Hopkins School of Medicine, Baltimore, Maryland 21218, USA
- 4Solomon Snyder Department of Neuroscience, Johns Hopkins School of Medicine, Baltimore, Maryland 21218, USA
- 5Department of Molecular Virology, Ohio State University, Columbus, Ohio 43210, USA
Abstract
Neuronal activity regulated pentraxin (Narp) is a secreted protein that regulates α-amino-3-hydroxyl-5-methyl-4-isoxazole-propionate receptors (AMPAR) aggregation and synaptogenesis. Mapping of Narp-positive neurons in brain has revealed it is prominently expressed in several limbic system projection pathways. Consistent with this localization pattern, Narp knockout mice show deficits in using the current value of a reinforcer to guide behavior, a critical function of the limbic system. To help assess whether this behavioral deficit is due to impairment of synaptogenesis during development or in modulating synaptic signaling in the mature brain, we have used a dominant negative Narp viral construct which blocks trafficking of endogenous Narp to axons. Focal injection of this viral construct into the medial prefrontal cortex (mPFC) of adult mice, a region containing Narp-positive projection neurons, blocked reinforcer devaluation. Thus, these results indicate that Narp released from mPFC neurons plays a key role in mediating synaptic changes underlying instrumental reinforcer devaluation.
Footnotes
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↵6 Corresponding author.
E-mail awj{at}jhu.edu; fax (410) 516-0494.
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[Supplemental material is available online at http://www.learnmem.org.]
- Received July 14, 2010.
- Accepted September 28, 2010.
- © 2010 Cold Spring Harbor Laboratory Press
