Temporal evolution of cortical ensembles promoting remote memory retrieval

• Published in: Nature neuroscience Vol. 22; no. 3; pp. 460 - 469
• Main Authors: DeNardo, Laura A., Liu, Cindy D., Allen, William E., Adams, Eliza L., Friedmann, Drew, Fu, Lisa, Guenthner, Casey J., Tessier-Lavigne, Marc, Luo, Liqun
• Format: Journal Article
• Language: English
• Published: New York Nature Publishing Group US 01.03.2019; Nature Publishing Group
• Subjects: 14/1; 14/19; 14/35; 14/63; 64/60; Analysis; Animal Genetics and Genomics; Animals; Behavioral Sciences; Biological Techniques; Biomedical and Life Sciences; Biomedicine; Brain; Cerebral Cortex - physiology; Comparative analysis; Conditioning, Classical; Cortex (temporal); Criticism; Fear; Hippocampus (Brain); Human-computer interaction; Integrases - metabolism; Labels; Learning; Learning - physiology; Memory, Long-Term - physiology; Mental Recall - physiology; Mice, Inbred C57BL; Mice, Transgenic; Neurobiology; Neurons; Neurons - physiology; Neurosciences; Prefrontal cortex; Prefrontal Cortex - physiology; Retrieval; Retrieval (Memory); Tamoxifen - administration & dosage; Time dependence
• ISSN: 1097-6256; 1546-1726
• DOI: 10.1038/s41593-018-0318-7

Memories of fearful events can last a lifetime. The prelimbic (PL) cortex, a subregion of prefrontal cortex, plays a critical role in fear memory retrieval over time. Most studies have focused on acquisition, consolidation, and retrieval of recent memories, but much less is known about the neural mechanisms of remote memory. Using a new knock-in mouse for activity-dependent genetic labeling ( TRAP2 ), we demonstrate that neuronal ensembles in the PL cortex are dynamic. PL neurons TRAPed during later memory retrievals are more likely to be reactivated and make larger behavioral contributions to remote memory retrieval compared to those TRAPed during learning or early memory retrieval. PL activity during learning is required to initiate this time-dependent reorganization in PL ensembles underlying memory retrieval. Finally, while neurons TRAPed during earlier and later retrievals have similar broad projections throughout the brain, PL neurons TRAPed later have a stronger functional recruitment of cortical targets. DeNardo et al. characterize TRAP2, which allows genetic access to neurons based on their activity, and use it to show that neuronal ensembles in prelimbic cortex for remote fear memory undergo dynamic changes during the first 14 days after learning.