biostudies-literaturePavlova IPNew York Stem Cell FoundationColumbia UniversityNational Alliance for Research on Schizophrenia and DepressionNIA NIH HHSBrain and Behavior Research FoundationNational Institutes of HealthNIH HHSNIGMS NIH HHS523-535https://www.ebi.ac.uk/biostudies/studies/S-EPMC6021204biostudies-literatureUnknown28(7)Recent genetic tools have allowed researchers to visualize and manipulate memory traces (i.e., engrams) in small brain regions. However, the ultimate goal is to visualize memory traces across the entire brain in order to better understand how memories are stored in neural networks and how multiple memories may coexist. Intact tissue clearing and imaging is a new and rapidly growing area of focus that could accomplish this task. Here, we utilized the leading protocols for whole-brain clearing and applied them to the ArcCreER^T2 mice, a murine line that allows for the indelible labeling of memory traces. We found that CLARITY and PACT greatly distorted the tissue, and iDISCO quenched enhanced yellow fluorescent protein (EYFP) fluorescence and hindered immunolabeling. Alternative clHippocampusOptimization of immunolabeling and clearing techniques for indelibly labeled memory traces.PMC6021204NARSAD Young Investigator GrantR01 AG043688DP5 OD017908NYSTEM C‐029157T32 GM007367Lanio MHen RPavlova IPShipley SCDenny CAfalseOptimization of immunolabeling and clearing techniques for indelibly labeled memory traces.Recent genetic tools have allowed researchers to visualize and manipulate memory traces (i.e., engrams) in small brain regions. However, the ultimate goal is to visualize memory traces across the entire brain in order to better understand how memories are stored in neural networks and how multiple memories may coexist. Intact tissue clearing and imaging is a new and rapidly growing area of focus that could accomplish this task. Here, we utilized the leading protocols for whole-brain clearing and applied them to the ArcCreER^T2 mice, a murine line that allows for the indelible labeling of memory traces. We found that CLARITY and PACT greatly distorted the tissue, and iDISCO quenched enhanced yellow fluorescent protein (EYFP) fluorescence and hindered immunolabeling. Alternative cl2018-01-01T00:00:00Z2018 Jul2026-05-01T03:19:59.055Z2026-04-07T16:34:22.735ZS-EPMC60212042966357810.1002/hipo.22951