• kainate-induced degeneration and death of CA3, CA1, and hilar neurons is accelerated and increased in mutants compared to wild-type

• cultured hippocampal neurons show increased susceptibility to death induced by glutamate, due to impaired calcium homeostasis, increased oxidative stress, and mitochondrial dysfunction

• homozygotes are hypersensitive to seizure-induced synaptic degeneration and necrotic neuronal death in the hippocampus

• homozygotes do not exhibit a deficit in contextual fear learning at 3 months of age (J:91277)

• homozygous mice do not differ in performance in Morris water maze or in contextual fear conditioning (J:99604)

• kainate-induced degeneration and death of CA3, CA1, and hilar neurons is accelerated and increased in mutants compared to wild-type

• cultured hippocampal neurons show increased susceptibility to death induced by glutamate, due to impaired calcium homeostasis, increased oxidative stress, and mitochondrial dysfunction

• kainate-induced degeneration and death of CA3, CA1, and hilar neurons is accelerated and increased in mutants compared to wild-type

• cultured hippocampal neurons show increased susceptibility to death induced by glutamate, due to impaired calcium homeostasis, increased oxidative stress, and mitochondrial dysfunction

• at E15 to E18

• limb ateliosis

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• in the central nervous system

• exhibit impaired hippocampus-dependent contextual fear learning at 3 months of age, showing reduced freezing behavior

• however, show normal cued fear learning, anxiety, motor coordination and shock threshold

• exhibit a 35% decrease in the number of newborn cells in the dentate gyrus of 3-month old mutants, indicating impaired adult neurogenesis

• exhibit a 35% decrease in the number of newborn cells in the dentate gyrus of 3-month old mutants, indicating impaired adult neurogenesis

• mutants attend less accurately to short, spatially unpredictable stimuli when the attentional demand of the task is high and also show a general tendency to make more perseverative responses than wild-type mice

• mutants initially respond as accurately as wild-type mice, however subsequently they fail to sustain their attention over the duration of the task, indicating reduced vigilance, or ability to sustain attention over a long period of time

• treatment of mice with the cholinesterase inhibitor donepezil results in an enhanced ability to sustain attention

• although born in Mendelian ratios, no mice survive to weaning

• mice do not exhibit the neuron loss or increase in microglial density and migration velocity observed in Cx3cr1^tm1Litt/Cx3cr1⁺ Psen1^tm1Mpm/Psen1^tm1Mpm Tg(APPSwe,tauP301L)1Lfa mice (J:159680)

• microglial density increases over time around lost neurons unlike in Cx3cr1^tm1Litt/Cx3cr1^tm1Litt Psen1^tm1Mpm/Psen1^tm1Mpm Tg(APPSwe,tauP301L)1Lfa mice

• microglia migration velocity around lost neurons is 2-fold greater than in Cx3cr1^tm1Litt heterozygotes and homozygotes

• of YFP+ layer III neurons at 4 to 6 months

• microglial density increases over time around lost neurons unlike in Cx3cr1^tm1Litt/Cx3cr1^tm1Litt Psen1^tm1Mpm/Psen1^tm1Mpm Tg(APPSwe,tauP301L)1Lfa mice

• microglia migration velocity around lost neurons is 2-fold greater than in Cx3cr1^tm1Litt heterozygotes and homozygotes

• microglial density increases over time around lost neurons unlike in Cx3cr1^tm1Litt/Cx3cr1^tm1Litt Psen1^tm1Mpm/Psen1^tm1Mpm Tg(APPSwe,tauP301L)1Lfa mice

• mice exhibit increased amyloid load compared with App^tm1Ck Psen1^tm1Mpm double homozygotes

• mice exhibit increased amyloid load compared with App^tm1Ck Psen1^tm1Mpm double homozygotes

• in Morris water mazed, learning of task is normal but retention is impaired; 6-month old mice require 6 days of training to achieve escape latency of >20 seconds, compared to 3 days in 2 month old control mice

• at 4 and 6 months, mice show longer escape latencies in the first daily trial relative to the last trial of the previous training day indicating day-to-day retention impairment; 2-month old mice do not show this impairment in retention

• short- (1.5 hr posttraining) and long-term (24 hr posttraining) spatial recognition memory in probe trials are impaired at 6 months, whereas 4-month old mice show similar performance at 1.5 hours and impaired retention at 24 hours

• after clearance of intraneuronal Abeta using antibodies, early retention deficits are ablated, whereas long-term retention remains impaired

• at 6 months, naive and trained mice display significantly impaired long- and short-term retention for contextual fear; at 4 months, mice have normal retention for short-term (1.5 hr) contextual fear but impaired memory of contextual fear at 24 hours

• at 6 months, extracellular Abeta plaques are observed in the cerebral cortex, and intracellular accumulation is seen in pyramidal neurons of the CA1 region of hippocampus and within basolateral amygdala and cortical neurons

• prominent intraneuronal Abeta accumulation is present at 4 months, preceding extracellular amyloid plaque formation

• treatment of mice with antibodies to Abeta results in clearance of intraneuroanl Abeta in hippocampus and cortex, but not in amygdala

• at 6 months, extracellular Abeta plaques are observed in the cerebral cortex, and intracellular accumulation is seen in pyramidal neurons of the CA1 region of hippocampus and within basolateral amygdala and cortical neurons

• prominent intraneuronal Abeta accumulation is present at 4 months, preceding extracellular amyloid plaque formation

• treatment of mice with antibodies to Abeta results in clearance of intraneuroanl Abeta in hippocampus and cortex, but not in amygdala

• tau pathology is detected initially by 6 months of age, and tangle pathology is advanced by 20 months

• Abeta oligomers begin to accumulate between 2 and 6 months of age, with continued age-dependent increase observed between 12 and 20 months

• intraneuronal oligomers are detected at 4-6 months of age

• Abeta oligomers begin to accumulate between 2 and 6 months of age, with continued age-dependent increase observed between 12 and 20 months

• intraneuronal oligomers are detected at 4-6 months of age

• mice accumulate more plaques than in Psen1^tm1.1Tcs/Psen1^tm1.1Tcs Tg(APPSWE)2576Kha mice

• mice accumulate more plaques than in Psen1^tm1.1Tcs/Psen1^tm1.1Tcs Tg(APPSWE)2576Kha mice