Neurobiology of Disease 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 themost common form ofmental retardation withmany 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 changeswere found inbasal synaptic transmission.This suggests that synapticplasticity in theACCandamygdalaofFMR1KOmiceplays an important role in the expression of behavioral phenotypes similar to the symptoms of fragile X syndrome. Key words: trace fear memory; long-term potentiation; cingulate cortex; amygdala; fragile X syndrome; attentio