ABCG1 over-expression does not impact spatial reference memory or synaptic plasticity. The Morris Water Maze was employed to assess spatial reference memory in wild-type (WT; n = 11) and ABCG1 BAC Tg (Tg; n = 11) animals. (A) Latency to platform. Each point represents an average of 4 daily trials during the training period. No significant difference was observed between the groups in the time taken to find the hidden platform. (B) Probe trial results from a single-trial test. Both control and ABCG1 over-expressing groups showed similar preference for the North (N) quadrant, which contained the platform on training trials. All p values are non-significant. (C) In vitro electrophysiology was performed on 350 μm thick hippocampal slices derived from aged mice over-expressing ABCG1 (Tg) and wild-type (WT) littermates. High frequency stimulation (HFS) was applied to the Schaeffer collaterals to induce LTP in the CA1 region. No significant difference was observed between wild-type and transgenic mice. (D) Two stimuli were applied to the Schaeffer collaterals, including paired-pulse facilitation in the CA1 region, before and after the HFS tetanus protocol. No significant differences were observed between wild-type and transgenic mice, indicating that presynaptic release was unaffected by HFS in either mouse phenotype.