ERIC Number: EJ921164
Record Type: Journal
Publication Date: 2011-Apr
Abstractor: As Provided
Reference Count: 0
Fragile X Mental Retardation Protein Regulates Heterosynaptic Plasticity in the Hippocampus
Connor, Steven A.; Hoeffer, Charles A.; Klann, Eric; Nguyen, Peter V.
Learning & Memory, v18 n4 p207-220 Apr 2011
Silencing of a single gene, FMR1, is linked to a highly prevalent form of mental retardation, characterized by social and cognitive impairments, known as fragile X syndrome (FXS). The FMR1 gene encodes fragile X mental retardation protein (FMRP), which negatively regulates translation. Knockout of Fmr1 in mice results in enhanced long-term depression (LTD) induced by metabotropic glutamate receptor (mGluR) activation. Despite the evidence implicating FMRP in LTD, the role of FMRP in long-term potentiation (LTP) is less clear. Synaptic strength can be augmented heterosynaptically through the generation and sequestration of plasticity-related proteins, in a cell-wide manner. If heterosynaptic plasticity is altered in Fmr1 knockout (KO) mice, this may explain the cognitive deficits associated with FXS. We induced homosynaptic plasticity using the [beta]-adrenergic receptor ([beta]-AR) agonist, isoproterenol (ISO), which facilitated heterosynaptic LTP that was enhanced in Fmr1 KO mice relative to wild-type (WT) controls. To determine if enhanced heterosynaptic LTP in Fmr1 KO mouse hippocampus requires protein synthesis, we applied a translation inhibitor, emetine (EME). EME blocked homo- and heterosynaptic LTP in both genotypes. We also probed the roles of mTOR and ERK in boosting heterosynaptic LTP in Fmr1 KO mice. Although heterosynaptic LTP was blocked in both WT and KOs by inhibitors of mTOR and ERK, homosynaptic LTP was still enhanced following mTOR inhibition in slices from Fmr1 KO mice. Because mTOR will normally stimulate translation initiation, our results suggest that [beta]-AR stimulation paired with derepression of translation results in enhanced heterosynaptic plasticity.
Descriptors: Animals, Mental Retardation, Depression (Psychology), Genetic Disorders, Neurological Impairments, Interpersonal Competence, Genetics, Metabolism, Neurological Organization, Cognitive Ability, Brain, Stimulation
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Publication Type: Journal Articles; Reports - Research
Education Level: N/A
Authoring Institution: N/A