Editor’s Pick: Molecular signatures for synaptic defects

New protein synthesis is essential for experience dependent learning. While two widely used mouse models—Fmr^-/y, for Fragile X Syndrome (FXS), and Syngap^+/-, for SYNGAP1-related intellectual disability (SRID)—both show excessive hippocampal protein synthesis, they differ in defects of synaptic plasticity.

In this paper, Aditi Singh et al. use Translating Ribosome Affinity Purification and RNA sequencing (TRAP-seq) to investigate the molecular environment of pyramidal neurons in hippocampal subregion CA1 of Syngap^+/- mutant mice. They report that the translating mRNA population shows upregulated long mRNAs. This suggests that Syngap^+/- mice have a persistent strengthening of synapses mimicking the effect of chemically induced long-term potentiation in wild-type mice. This effect is opposite to what they observed when comparing their data to those currently available for the Fmr^-/y mouse model of FXS, which instead show enrichment of mRNAs mimicking metabotropic glutamate receptor-mediated long-term depression in wild-type mice.

The findings in this study are very important, as they demonstrate how altered capacity for plasticity in different mouse models of intellectual developmental disability may depend on distinct molecular signatures in CA1 pyramidal neurons.

— Arianna Maffei, Reviewing Editor

Read the full article:

Syngap^+/- CA1 pyramidal neurons exhibit upregulated translation of long mRNAs associated with LTP
Aditi Singh, Manuela Rizzi, Sang S. Seo, and Emily K. Osterweil