Abstract
Background
Despite our understanding of the significance of the prefrontal cortex in the consolidation
of long-term memories, its role in the encoding of long-term memories remains elusive.
Here we investigated the role of new protein synthesis in the mouse medial prefrontal
cortex (mPFC) in encoding contextual fear memory.
Methods
Because a change in the association of messenger RNAs (mRNAs) to polyribosomes is
an indicator of new protein synthesis, we assessed the changes in polyribosome-associated
mRNAs in the mPFC following contextual fear conditioning (CFC) in the mouse. Differential
gene expression in the mPFC was identified by polyribosome profiling (n = 18). The role of new protein synthesis in the mPFC was determined by focal inhibition
of protein synthesis (n = 131) and by intraprelimbic cortex manipulation (n = 56) of Homer3, a candidate identified from polyribosome profiling.
Results
We identified several mRNAs that are differentially and temporally recruited to polyribosomes
in the mPFC following CFC. Inhibition of protein synthesis in the prelimbic (PL) cortex
but not in the anterior cingulate cortex region of the mPFC immediately after CFC
disrupted encoding of contextual fear memory. Intriguingly, inhibition of new protein
synthesis in the PL cortex 6 hours after CFC did not impair encoding. Furthermore,
expression of Homer3, an mRNA enriched in polyribosomes following CFC, in the PL cortex
constrained encoding of contextual fear memory.
Conclusions
Our studies identify several molecular substrates of new protein synthesis in the
mPFC and establish that encoding of contextual fear memories require new protein synthesis
in PL subregion of mPFC.
Keywords
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Article info
Publication history
Published online: October 21, 2016
Accepted:
October 4,
2016
Received in revised form:
October 3,
2016
Received:
September 14,
2016
Identification
Copyright
© 2016 Society of Biological Psychiatry. Published by Elsevier Inc. All rights reserved.
