Localized disruption of Narp in medial prefrontal cortex blocks reinforcer devaluation performance.
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.
Department of Psychological and Brain Sciences, Johns Hopkins University, Baltimore, Maryland 21218, USA. awj@jhu.edu
Alexander W
AW
Johnson
Sungho
S
Han
Ashley M
AM
Blouin
Jasjit
J
Saini
Paul F
PF
Worley
Matthew J
MJ
During
Peter C
PC
Holland
Jay M
JM
Baraban
Irving M
IM
Reti
D000704:Analysis of Variance; D000818:Animals; D001522:Behavior, Animal; D002097:C-Reactive Protein / Q000172:deficiency / Q000378:metabolism*; D002772:Cholera Toxin / Q000378:metabolism; D003216:Conditioning, Operant / Q000502:physiology*; D005822:Genetic Vectors / Q000378:metabolism; D008164:Luminescent Proteins / Q000235:genetics; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009419:Nerve Tissue Proteins / Q000172:deficiency / Q000378:metabolism*; D009434:Neural Pathways / Q000502:physiology; D009714:Nucleus Accumbens / Q000502:physiology; D017397:Prefrontal Cortex / Q000378:metabolism*; D012054:Reinforcement, Psychology; D000099153:Pentraxins
D002097:C-Reactive Protein; D002772:Cholera Toxin; D008164:Luminescent Proteins; D009419:Nerve Tissue Proteins; D000099153:Pentraxins