Increased prefrontal cortex neurogranin enhances plasticity and extinction learning

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


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.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Analysis of Variance
  • Animals
  • Calcium / metabolism
  • Calcium-Calmodulin-Dependent Protein Kinase Type 2 / genetics
  • Calcium-Calmodulin-Dependent Protein Kinase Type 2 / metabolism
  • Conditioning, Classical / physiology
  • Conditioning, Operant / physiology
  • Electric Stimulation
  • Extinction, Psychological / physiology*
  • Fear / physiology
  • In Vitro Techniques
  • Long-Term Potentiation / genetics
  • Male
  • Mice
  • Mice, Transgenic
  • Neurogranin / genetics
  • Neurogranin / metabolism*
  • Neuronal Plasticity / genetics*
  • Prefrontal Cortex / cytology
  • Prefrontal Cortex / physiology*
  • Pyramidal Cells / metabolism
  • Sucrose / administration & dosage


  • Neurogranin
  • Sucrose
  • Calcium-Calmodulin-Dependent Protein Kinase Type 2
  • Calcium