nervous system
N |
• homozygotes show no changes in indirect measures of presynaptic release probability, as paired-pulse facilitation and the rate of decay of NMDAR-mediated excitatory postsynaptic currents in the presence of MK-801 are normal
• no changes in multiple measures of brain size, embryonic and adult brain cell proliferation, neurogenesis, or cortical layering/migration are observed
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• CA1 pyramidal neurons show a significant reduction in dendritic spine density
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• CA1 pyramidal neurons show a significant reduction in dendritic length, branching complexity, and dendritic spine density
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• homozygotes show a reduction in functional excitatory synapse number
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• homozygotes show significantly reduced synaptic transmission in the CA1 region of the hippocampus relative to wild-type controls
• reduced synaptic transmission correlates with increased levels of RhoA (ras homolog family member A), a KCTD13/CUL3 ubiquitin ligase substrate, after P7 and is reversed by RhoA inhibition
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• homozygotes show a ~50% reduction of field excitatory postsynaptic potential (fEPSP) slope relative to wild-type controls
• hippocampal slice incubation with a RhoA/B/C inhibitor (rhosin or C3) reverses the fEPSP slope deficit to vehicle-treated wild-type levels
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• miniature excitatory postsynaptic current (mEPSC) frequency is significantly decreased in CA1 pyramidal neurons relative to wild-type controls, with no change in the amplitude of mEPSCs
• mEPSC frequency is significantly decreased in somatosensory cortical layer 2/3 neurons, with no change in the amplitude of mEPSCs
• hippocampal slice incubation with the RhoA/B/C inhibitor rhosin rescues the reduction in mEPSC frequency to vehicle-treated wild-type levels
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• miniature inhibitory postsynaptic current (mIPSC) frequency is significantly decreased in somatosensory cortical layer 2/3 neurons relative to wild-type controls; however, CA1 pyramidal neuron mIPSC amplitude is normal
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behavior/neurological
• homozygotes show increased locomotor activity relative to wild-type controls, as determined by the total number of photobeam breaks over a 2 hr period
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growth/size/body
N |
• homozygotes exhibit normal body weight at 12 weeks of age
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