<i>Syngap^+/-</i> CA1 Pyramidal Neurons Exhibit Upregulated Translation of Long MRNAs Associated with LTP.

ABSTRACT: In the Syngap^+/- model of SYNGAP1-related intellectual disability (SRID), excessive neuronal protein synthesis is linked to deficits in synaptic plasticity. Here, we use Translating Ribosome Affinity Purification and RNA-seq (TRAP-seq) to identify mistranslating mRNAs in Syngap^+/- CA1 pyramidal neurons that exhibit occluded long-term potentiation (LTP). We find the translation environment is significantly altered in a manner that is distinct from the Fmr1^-/y model of fragile X syndrome (FXS), another monogenic model of autism and intellectual disability. The Syngap^+/- translatome is enriched for regulators of DNA repair and mimics changes induced with chemical LTP (cLTP) in WT. This includes a striking upregulation in

SUBMITTER: Singh A 

PROVIDER: S-EPMC12091090 | biostudies-literature | 2025 May

REPOSITORIES: biostudies-literature