behavior/neurological
• mice show less conditioned contextual freezing during the test phase of the fear conditioning test
• however, no differences in the open field or elevated plus maze are seen indicating normal basal locomotor activity and levels of anxiety or reaction to novelty
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• in the fear conditioning test, mice are slower in associating an auditory tone (conditioned stimulus) with a foot shock (unconditioned stimulus)
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• 10-14-week-old mice show slower spatial memory acquisition during the Morris water maze training phase
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• 10-14-week-old mice spend less time in the target quadrant during the Morris water maze probe trial
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• in the reverse learning test, during which the platform is moved to a new location, mice exhibit slower learning of the new platform location, indicating impaired cognitive flexibility
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nervous system
• hippocampal neurons show impaired excitatory synapse maturation
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• hippocampus CA1 neurons show a reduction in spine density and head volume, indicating defective synapse development
• however, dendritic arborization is not affected
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• hippocampus neurons show impaired excitatory synapse development
• primary embryonic hippocampus neurons show a reduced density of PSD95+, GluN1+, and GluA1+ puncta and decreased colocalization of pre-/post-synaptic and AMPA/NMDA markers, indicating reduction in the number of functional excitatory synapses
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• CA1 neurons from young adults (12-14 weeks old) show reduced spontaneous miniature excitatory postsynaptic currents (mEPSCs) amplitude, with more mEPSCs amplitudes clustered to the lower amplitude bins
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• mEPSC frequency is decreased in CA1 neurons
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• overall reduction in postsynaptic fEPSP response to presynaptic inputs in CA1 responses, while paired pulse ratio responses across various inter-stimulus intervals are not altered
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• decrease in AMPA/NMDA receptor current ratio in CA1 neurons
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• reduction of long-term potentiation (LTP) from CA1 region
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• reduction of long-term depression (LTD) from CA1 region
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