nervous system
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• mice show no major alterations in gross hippocampus and cerebellum structure or in the thickness of the different layers of the hippocampus CA1 region
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• mice show deficits in polysialylation of locally secreted NCAM in distal dendrites of the stratum lacunosum moleculare (SLM)
• however, levels of NCAM and of major polysialyltransferases involved in NCAM polysialylation are normal, suggesting that reduced PSA-NCAM levels in distal dendrites of the SLM are likely due to a reduced number of Golgi satellites
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• in culture, primary hippocampal neurons show a significant reduction in Golgi length and a significantly lower % of neurons with extended Golgi than wild-type neurons
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• pyramidal cells of the CA1 region show a mild non-significant reduction in Golgi length that is largely due to a decreased number of neurons endowed with an extended Golgi
• however, no major changes in the morphology of the somatic Golgi are observed
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• following delivery of two viruses (AAV9-EF1alpha-LoxP-EGFP-LoxP and AAV9-CaMKII-Cre) to the CA1 hippocampal region, pyramidal neurons show a significant reduction in spine density toward distal dendrites in the SLM but not in other strata
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• CA1 pyramidal neurons show significantly reduced NCAM polysialylation levels in distal dendrites of the stratum radiatum distal (SRD) and stratum lacunosum moleculare (SLM)
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• mice exhibit impaired long-term synaptic plasticity in distal dendrites of temporoammonic connections to CA1-SLM
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• fEPSP amplitude is reduced by 40% whether in response to stimulation of the Schaffer collateral-CA1 pathway (SC-CA1) or in response to stimulation of the temporoammonic-CA1 (TA-CA1) pathway, indicating deficits in basal transmission in proximal and distal dendrites
• however, paired-pulse facilitation is normal
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• LTP induction in the TA-CA1 pathway to dendrites in the SLM is significantly impaired whereas LTP induction in the SC-CA1 pathway is normal, indicating a selective deficit in LTP at distal but not at more proximal dendrites of CA1 neurons
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