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J Neurosci. 2015 May 13;35(19):7503-8. doi: 10.1523/JNEUROSCI.0274-15.2015.

Increased prefrontal cortex neurogranin enhances plasticity and extinction learning.

Author information

1
Departments of Cell Biology, Neurobiology and Anatomy, Neuroscience Research Center, and.
2
Molecular & Behavioral Neuroscience Institute and.
3
Neuroscience Research Center, and Department of Pharmacology, Medical College of Wisconsin, Milwaukee, Wisconsin 53132.
4
Departments of Cell Biology, Neurobiology and Anatomy.
5
Molecular & Behavioral Neuroscience Institute and Department of Molecular and Integrative Physiology, University of Michigan Medical School, Ann Arbor, Michigan 48109.
6
Departments of Cell Biology, Neurobiology and Anatomy, Neuroscience Research Center, and ngerges@mcw.edu.

Abstract

Increasing plasticity in neurons of the prefrontal cortex (PFC) has been proposed as a possible therapeutic tool to enhance extinction, a process that is impaired in post-traumatic stress disorder, schizophrenia, and addiction. To test this hypothesis, we generated transgenic mice that overexpress neurogranin (a calmodulin-binding protein that facilitates long-term potentiation) in the PFC. Neurogranin overexpression in the PFC enhanced long-term potentiation and increased the rates of extinction learning of both fear conditioning and sucrose self-administration. Our results indicate that elevated neurogranin function within the PFC can enhance local plasticity and increase the rate of extinction learning across different behavioral tasks. Thus, neurogranin can provide a molecular link between enhanced plasticity and enhanced extinction.

KEYWORDS:

CaMKII; calmodulin; extinction; neurogranin; prefrontal cortex

PMID:
25972176
PMCID:
PMC4429154
DOI:
10.1523/JNEUROSCI.0274-15.2015
[Indexed for MEDLINE]
Free PMC Article

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