Increased prefrontal cortex neurogranin enhances plasticity and extinction learning

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 n...

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Bibliographic Details
Published in:The Journal of neuroscience 2015-05, Vol.35 (19), p.7503-7508
Main Authors: Zhong, Ling, Brown, Joshua, Kramer, Audra, Kaleka, Kanwardeep, Petersen, Amber, Krueger, Jamie N, Florence, Matthew, Muelbl, Matthew J, Battle, Michelle, Murphy, Geoffrey G, Olsen, Christopher M, Gerges, Nashaat Z
Format: Article
Language:English
Subjects:
Analysis of Variance
Animals
Brief Communications
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
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Summary: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.
ISSN:0270-6474
1529-2401
DOI:10.1523/JNEUROSCI.0274-15.2015