Deficits in trace fear memory and long-term potentiation in a mouse model for fragile X syndrome.
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.
Zhao
Ming-Gao
MG
Department of Physiology, Faculty of Medicine, University of Toronto, Toronto, Ontario, M5S 1A8, Canada.
Toyoda
Hiroki
H
Ko
Shanelle W
SW
Ding
Hoi-Ki
HK
Wu
Long-Jun
LJ
Zhuo
Min
M
D000679:Amygdala / Q000503:physiopathology; D000818:Animals; D001007:Anxiety / Q000209:etiology; D004195:Disease Models, Animal; D019706:Excitatory Postsynaptic Potentials; D005239:Fear; D051860:Fragile X Messenger Ribonucleoprotein 1 / Q000235:genetics*; D005600:Fragile X Syndrome / Q000235:genetics / Q000503:physiopathology* / Q000523:psychology*; D006179:Gyrus Cinguli / Q000503:physiopathology; D017774:Long-Term Potentiation; D008297:Male; D008569:Memory Disorders / Q000209:etiology*; D051379:Mice; D018345:Mice, Knockout; D009619:Nociceptors / Q000503:physiopathology; D016194:Receptors, N-Methyl-D-Aspartate / Q000378:metabolism; D013569:Synapses; D009435:Synaptic Transmission
D051860:Fragile X Messenger Ribonucleoprotein 1; D016194:Receptors, N-Methyl-D-Aspartate; C497684:Fmr1 protein, mouse