RT Journal Article
SR Electronic
T1 Fear Learning Induces Long-Lasting Changes in Gene Expression and Pathway Specific Presynaptic Growth
JF bioRxiv
FD Cold Spring Harbor Laboratory
SP 571331
DO 10.1101/571331
A1 Blythe C. Dillingham
A1 Peter Cameron
A1 Simon Pieraut
A1 Leonardo M. Cardozo
A1 Eun J. Yoo
A1 Anton Maximov
A1 Lisa Stowers
A1 Mark Mayford
YR 2019
UL http://biorxiv.org/content/early/2019/03/09/571331.abstract
AB The stabilization or consolidation of long-term memories lasting more than a few hours requires new gene expression. While neural activity has been shown to induce expression of a variety of genes within several hours of learning, whether this leads to persistent changes in gene expression that lasts for days or weeks remains unclear. We developed a novel mouse line which expresses Cre recombinase in an inducible manner and used it to examine gene expression in learning-activated neurons of the medial prefrontal cortex (mPFC) one month following contextual fear conditioning. The mPFC is not required for the initial retrieval of contextual memory but becomes necessary after one month, suggesting a slowly developing plasticity. We found a variety of changes in gene expression in learning-activated neural ensembles that were specific to the mPFC. One group of transcriptional changes observed was the coordinated upregulation of presynaptic proteins suggesting a potential learning-induced elaboration of presynaptic terminals. We tested this idea by labeling the projections of mPFC neurons active during initial learning and found an increase in the number of terminals in neurons projecting to the basolateral amygdala at 1 month following training. These results suggest a presynaptic growth mechanism that could account for the enhanced role of the mPFC in fear memory retrieval at long time points after learning.