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Defective memory engram reactivation underlies impaired fear memory recall in Fragile X syndrome
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Defective memory engram reactivation underlies impaired fear memory recall in Fragile X syndrome
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Journal Article
Defective memory engram reactivation underlies impaired fear memory recall in Fragile X syndrome
2020
Overview
Fragile X syndrome (FXS) is an X chromosome-linked disease associated with severe intellectual disabilities. Previous studies using the
Fmr1
knockout (KO) mouse, an FXS mouse model, have attributed behavioral deficits to synaptic dysfunctions. However, how functional deficits at neural network level lead to abnormal behavioral learning remains unexplored. Here, we show that the efficacy of hippocampal engram reactivation is reduced in
Fmr1
KO mice performing contextual fear memory recall. Experiencing an enriched environment (EE) prior to learning improved the engram reactivation efficacy and rescued memory recall in the
Fmr1
KO mice. In addition, chemogenetically inhibiting EE-engaged neurons in CA1 reverses the rescue effect of EE on memory recall. Thus, our results suggest that inappropriate engram reactivation underlies cognitive deficits in FXS, and enriched environment may rescue cognitive deficits by improving network activation accuracy.
Publisher
eLife Science Publications, Ltd,eLife Sciences Publications, Ltd,eLife Sciences Publications Ltd
Subject
/ Animals
/ Estrogen Antagonists - pharmacology
/ Fragile X Mental Retardation Protein - genetics
/ Fragile X Mental Retardation Protein - metabolism
/ Fragile X Syndrome - genetics
/ Fragile X Syndrome - physiopathology
/ Gene Expression Regulation - drug effects
/ Male
/ Memory
/ Mice
/ Neurons
