nervous system
• at P19-P25, excitatory transmission in Schaffer collateral-CA1 pyramidal (SC-CA1) synapses is significantly reduced relative to those at wild-type synapses, as measured by the input-output relationship
• mice show a reduced excitation/inhibition (E/I) ratio in the hippocampal CA1 region but an increased E/I ratio in pyramidal neurons of the medial prefrontal cortex (mPFC), indicating distinct alterations of the E/I ratio in different brain regions
• however, paired pulse ratios at SC-CA1 synapses are normal at P19-P25, and long-term potentiation (LTP) induced by high-frequency stimulation is similar to that of wild-type SC-CA1 synapses at P21-P24
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• at P19-P25, mice show reduced excitatory synaptic transmission at hippocampal SC-CA1 synapses, as measured by plots of field excitatory postsynaptic potential (fEPSP) slopes against fiber volley amplitudes (input-output)
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• at P23-P27, the frequency, but not the amplitude, of miniature inhibitory postsynaptic currents (mIPSCs) is significantly increased in hippocampal CA1 pyramidal cells relative to wild-type neurons
• in contrast, at P39-P54, the frequency, but not the amplitude, of mIPSCs is significantly decreased in layer 2/3 pyramidal neurons in the prelimbic area of the mPFC relative to wild-type neurons
• however, both the amplitude and frequency of miniature excitatory postsynaptic currents (mEPSCs) are normal in CA1 pyramidal cells at P19-P22 as well as in mPFC prelimbic layer 2/3 pyramidal neurons at P39-P54
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behavior/neurological
N |
• mice show normal levels of social interaction, social novelty recognition, separation-induced pup ultrasonic vocalization, novel object recognition, and locomotor activity in both novel and familiar environments relative to wild-type controls
• mice do not exhibit altered anxiety-like behavior or repetitive behaviors such as grooming relative to wild-type controls
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• although escape latency, target quadrant occupancy scores, and swimming speed are largely normal, mice display a decreased number of exact platform crossings during the probe phase of the Morris water maze test relative to wild-type controls, indicating that spatial memory is mildly impaired
• however, in the reversal-learning water maze paradigm, mice perform normally during the reversal-learning and probe phases with no differences in the number of platform crossings
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• although mice show normal novel-object preference in the novel object recognition test, total time spent exploring novel plus familiar objects is significantly reduced on day 2 relative to wild-type controls
• however, total locomotion during the test phase is normal
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• mice display a mild increase in rearing behavior in a novel home-cage-like environment, as determined by behavioral monitoring for 3 consecutive days with normal light-dark cycles
• rearing is significantly increased during the first 2 hrs on day 1, but not on days 2 or 3, relative to wild-type controls
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