Mildly impaired water maze performance in maleFmr1 knockout mice

D’Hooge, Rudi; Nagels, Guy; Franck, F.; Bakker, Cathy; Reyniers, Edwin; Storm, Katrien; Kooy, R. Frank; Oostra, Ben A.; Willems, Patrick J.; Deyn, Peter Paul De

doi:10.1016/s0306-4522(96)00224-2

Cited by 185 publications

(162 citation statements)

References 26 publications

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“…Four independent studies showed that LTP in the CA1 region of the hippocampus was unaltered in FMR1 KO mice (Godfraind et al, 1996;Paradee et al, 1999;Li et al, 2002), despite reported deficits in hippocampal-dependent spatial memory and contextual fear memory (D'Hooge et al, 1997;Paradee et al, 1999;Van Dam et al, 2000;Bakker and Oostra, 2003) (Table 1). Another study reported a reduction in LTP within the somatosensory cortex of FMR1 KO mice (Li et al, 2002).…”

Section: Discussionmentioning

confidence: 99%

Deficits in Trace Fear Memory and Long-Term Potentiation in a Mouse Model for Fragile X Syndrome

Zhao¹,

Toyoda²,

Ko³

et al. 2005

J. Neurosci.

265

272

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Trace fear memory requires the activity of the anterior cingulate cortex (ACC) and is sensitive to attention-distracting stimuli. Fragile X syndrome is the most common form of mental retardation with many patients exhibiting attention deficits. Previous studies in fragile X mental retardation 1 (FMR1) knock-out (KO) mice, a mouse model for fragile X, focused mainly on hippocampal-dependent plasticity and spatial memory. We demonstrate that FMR1 knock-out mice show a defect in trace fear memory without changes in locomotion, anxiety, and pain sensitivity. Whole-cell path-clamp recordings in the ACC show that long-term potentiation (LTP) was completely abolished. A similar decrease in LTP was found in the lateral amygdala, another structure implicated in fear memory. No significant changes were found in basal synaptic transmission. This suggests that synaptic plasticity in the ACC and amygdala of FMR1 KO mice plays an important role in the expression of behavioral phenotypes similar to the symptoms of fragile X syndrome.

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Section: Discussionmentioning

confidence: 99%

Deficits in Trace Fear Memory and Long-Term Potentiation in a Mouse Model for Fragile X Syndrome

Zhao¹,

Toyoda²,

Ko³

et al. 2005

J. Neurosci.

265

272

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show abstract

“…However, previous studies have shown that learning may be normal, 8,30,31 mildly impaired, 7,[30][31][32][33] or even improved 34 in Fmr1-KO mice. However, there are many different types of learning, 35 and the Fmr1-KO mutation may affect some forms more than others.…”

Section: Fmr1-ko Mice Exhibit Enhanced Ppimentioning

confidence: 91%

Sensorimotor gating abnormalities in young males with fragile X syndrome and Fmr1-knockout mice

et al. 2004

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Fragile X syndrome (FXS) is the most common single gene (FMR1) disorder affecting cognitive and behavioral function in humans. This syndrome is characterized by a cluster of abnormalities including lower IQ, attention deficits, impairments in adaptive behavior and increased incidence of autism. Here, we show that young males with FXS have profound deficits in prepulse inhibition (PPI), a basic marker of sensorimotor gating that has been extensively studied in rodents. Importantly, the magnitude of the PPI impairments in the fragile X children predicted the severity of their IQ, attention, adaptive behavior and autistic phenotypes. Additionally, these measures were highly correlated with each other, suggesting that a shared mechanism underlies this complex phenotypic cluster. Studies in Fmr1-knockout mice also revealed sensorimotor gating and learning abnormalities. However, PPI and learning were enhanced rather than reduced in the mutants. Therefore, these data show that mutations of the FMR1 gene impact equivalent processes in both humans and mice. However, since these phenotypic changes are opposite in direction, they also suggest that murine compensatory mechanisms following loss of FMR1 function differ from those in humans.

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“…These acquisition deficits have been replicated (106), but not consistently (75,174). Similarly, deficits in reversal learning in Fmr1 KO mice were replicated in some studies (106,193), but not all (75). Based on the variable results across laboratories, the spatial learning deficits identified in earlier studies may require very specific conditions in order to reproduce these results.…”

Section: Cognitive Deficitsmentioning

confidence: 94%