Analysis Tools
behavior/neurological
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• mice show no significant alterations in motor activities (open-field test), anxiety-like behavior (light-dark box transition test and elevated-plus maze test) or depressive-like behavior (tail suspension test) relative to wild-type controls
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• under a moderate training protocol, mice exhibit a smaller freezing response during inter-trial intervals but not when the tone is delivered; 24 hours after conditioning, mice show deficits in contextual but not auditory fear memory
• under a weaker training protocol, contextual but not auditory fear memory is impaired 2 hours after training
• injection of adult mice with AAV-YTHDF1 restores contextual fear memory to normal levels
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• in the hidden-platform version of the Morris water-maze test, mice spend a longer time navigating to the platform than wild-type controls; however, no differences are observed in visible platform training
• adult mice injected with AAV-YTHDF1 (to selectively re-express YTHDF1 in the hippocampus) show markedly enhanced spatial learning in the Morris water-maze test
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• in the Morris water-maze probe test, mice fail to remember the previous platform location, spending a similar time in each quadrant despite normal swimming activity, suggesting defects in spatial memory
• adult mice injected with AAV-YTHDF1 show markedly enhanced memory performance in the Morris water-maze test
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nervous system
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• mice show no significant alterations in gross hippocampal histology, adult hippocampal neurogenesis or cortical morphology relative to wild-type controls
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• hippocampal CA1 neurons from adult mice show reduced dendritic spine density but normal spine size (head diameter)
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• hippocampal CA1 neurons from adult mice show reduced dendritic spine density but normal spine size (head diameter)
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• mice exhibit impaired plasticity in hippocampal synapses
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• after high-frequency stimulation (HFS), average field excitatory postsynaptic potential (fEPSP) amplitude is reduced in the CA1 region of acute hippocampal slices
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• after 2 rounds of high-frequency stimulation (HFS), LTP is impaired in the CA1 region of acute hippocampal slices; late-phase LTP is also impaired after 4 rounds of HFS
• key LTP-related protein levels are reduced in hippocampal postsynaptic density (PSD) fractions
• injection of adult mice with AAV-YTHDF1 reverses the hippocampal LTP deficit
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• whole-cell patch-clamp recordings of hippocampal CA1 neurons show that spontaneous mEPSCs are markedly decreased in amplitude and frequency relative to control neurons
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• analysis of paired-pulse ratios (PPRs) demonstrates reduced presynaptic release probability in hippocampal CA1 neurons, indicating impaired basal synaptic transmission
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homeostasis/metabolism
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• after potassium chloride (KCl) depolarization, cultured hippocampal neurons exhibit significantly less nascent protein synthesis than KCl-stimulated wild-type neurons
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cellular
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• after potassium chloride (KCl) depolarization, cultured hippocampal neurons exhibit significantly less nascent protein synthesis than KCl-stimulated wild-type neurons
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