Analysis Tools
behavior/neurological
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• after a training session of three trials, homozygotes show impaired motor skill learning in a rotarod test; the mean performance in the first trial of each of five consecutive sessions revealed a significantly shorter latency to fall than wild-type controls
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• in a visual object recognition test, homozygotes spend the same time exploring the novel object and the familiar one, both at 1 hr and at 24 hrs after habituation and familiarization, unlike wild-type controls where the mean exploration time is significantly higher for the novel object than for the familiar one at both time points
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nervous system
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• at 1 month of age, mutant cortical (layer V) and hippocampal (CA1) pyramidal neurons exhibit a lower frequency of dendrites with high spine density relative to wild-type neurons
• the neck length of mushroom-shaped spines is significantly decreased both in the stratum radiatum of hippocampus CA1 area and in layer V of the S1 cortex
• the head diameter of mushroom spines is significantly reduced in mutant cortices but normal in the hippocampus
• in culture, primary hippocampal neurons from mutant embryos show a significantly reduced number of mature mushroom spines without any concomitant increase in dendritic filopodia, and abnormal organization of synapse-associated F-actin clusters which appear abnormally elongated and run parallel to the dendritic shaft membrane rather than protruding from it
• treatment with Src inhibitor SU6656 restores normal F-actin organization, with near complete disappearance of the elongated membrane-associated F-actin and with the appearance of actin-enriched mushroom spines
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• electrophysiological testing of perirhinal cortex revealed impaired synaptic plasticity
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• homozygotes exhibit reduced basal synaptic transmission in the perirhinal cortex
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• the evoked field response upon progressive increase of the stimulation amplitude is significantly lower than that in wild-type controls
• also, the normalized EPSP response amplitude at 50% of range is significantly lower than that in wild-type controls
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• although LTP is normally induced, the level of LTP falls to baseline at 1 hr after theta burst stimulus, unlike in wild-type control slices; in the last 15 min of registration, response levels are still potentiated in control slices, but return to baseline in mutant slices
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• homozygotes display reduced LTD relative to wild-type controls
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