Our data indicate that prophylactic ketamine may be protective against a stressor by altering neural activity, specifically the neural ensembles representing an individual stressor in vCA3.
Recent studies have focused on the identification and manipulation of memory traces in rodent models. The two main mouse models utilized are either a CreERT2/loxP tamoxifen (TAM)- or a tetracycline transactivator (tTA)/tetracycline-response element (TRE) doxycycline (DOX)-inducible system. These systems, however, could be improved to label a more specific population of activated neurons corresponding to behavior. Here, we sought to identify an improved selective estrogen receptor (ER) modulator (SERM) in which we could label an individual memory trace in ArcCreERT2 mice. We found that 4-hydroxytamoxifen (4-OHT) is the most selective SERM in the ArcCreERT2 x ROSA26-CAG-stopflox-channelrhodospin (ChR2)-enhanced yellow fluorescent protein (eYFP) mice. The half-life of 4-OHT is also shorter than TAM, allowing for more specificity of memory trace labeling. Furthermore, 4-OHT allowed for context-specific labeling in the dentate gyrus (DG) and CA3. In summary, we believe 4-OHT improves the specificity of memory trace labeling and will allow for refined memory trace studies in the future.
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