| Abstrakt: |
Background: Everyday learning involves higher order associations (HOA) across new and old experiences when a response is encoded without reinforcement. However, the neural and behavioral mechanisms of HOA‐based learning during remote memory retrieval are unknown. Method: We implement novel behavior to test the neural and behavioral mechanisms of HOA during remote memory retrieval. We train the animals in context A and sequentially test these animals for remote retrieval in same (A), similar(B), or novel (C) context, while invoking HOA‐based learning to investigate the neural correlates of HOA using hippocampal lesions, chemo genetics, and 2‐photon in vivo imaging. Result: Cohorts of AD mice show overall differences in freezing vs. controls (1‐w ANOVA, P>F = 1.48E‐11, n = 5). Subgroups of AD (n = 12) and control (n = 14) mice during remote retrieval in BAC show overall difference (1‐w ANOVA, P>F = 4.59E‐6), with AD mice showing similar freezing in B and A (t = ‐0.70). Freezing in C is different for control mice in ABC vs. BAC order (P>F = 1.84E‐8, n = 5,14) whereas, interestingly, AD mice show similar increase in C freezing on Day3 of remote testing for ABC vs. BAC testing orders (P>F = n.s, n = 5, 12). AD (n = 3) and WT (n = 4) mice were trained with tone and tested after 70 days. Freezing before and during the tone was significantly different for WT mice (1‐t Paired‐sample‐t‐test, P
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