Analysis Tools
behavior/neurological
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• in an open field assay, adult males show no differences in path length or thigmotaxis relative to wild-type controls, indicating normal locomotion and anxiety
• in a Y-maze test of spontaneous alternation, males show a normal number of successful spontaneous alternations over total arm entries, indicating normal working memory
• in an acoustic startle response assay, adult males perform similar to wild-type controls, ruling out an auditory deficit
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• in a single shock contextual fear-conditioning paradigm, males freeze significantly less often than wild-type controls during contextual recall
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• in a cued fear-conditioning paradigm, males show normal freezing behavior during training/acquisition but fail to significantly increase their freezing in response to the first tone cue during the recall session, indicating a deficit in the consolidation of long-term fear memory
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• in an object location memory (OLM) test, adult males show a significantly lower discrimination index than wild-type controls, indicating poor consolidation of spatial memories
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cellular
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• 30 min after single-shock contextual fear-conditioning (FC), males show impaired histone acetylation in the dorsal hippocampus, with significant decreases in H3K9ac and H4K5ac relative to wild-type FC controls and no significant upregulation of H4K5ac under FC relative to H4K5ac at baseline
• after FC, expression of key learning and memory-related genes is reduced in the dorsal hippocampus
• however, other histone acetylation sites (e.g. H3K18ac and H3K23ac) show no fluctuations under FC conditions and acetylation of histone H2B is unaffected
• moreover, no significant changes are noted in histone acetylation or in the hippocampal transcriptome under baseline conditions
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nervous system
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• H&E staining of hippocampal sections shows no gross anatomical defects in the brain of adult males
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