Altered striatal long-term potentiation in the eIF4E-TG mouse model of autism spectrum disorder

Autism spectrum disorder (ASD) is associated with deficits in synaptic plasticity across multiple brain regions. While striatal dysfunction is observed in several ASD mouse models, the effects of ASD-associated genes on striatal plasticity remain poorly understood. We previously showed that overexpression of the Simons Foundation Autism Research Initiative (SFARI) ASD risk gene eukaryotic initiation factor 4E (eIF4E) in transgenic (eIF4E-TG) mice produces ASD-like behaviors and impairs dorsal striatal dopamine release. Here, we examined whether eIF4E overexpression alters striatal synaptic transmission and plasticity. eIF4E-TG mice exhibited increased dendritic spine density, elevated AMPA- and NMDA receptor-mediated miniature excitatory postsynaptic current (mEPSC) frequency, and reduced AMPA mEPSC amplitude. In addition, spiny projection neurons (SPNs) showed enhanced induction and magnitude of NMDA receptor-dependent long-term potentiation (LTP) that was not prevented by D1 or D2 receptor antagonism. Finally, depolarization-evoked somatic and dendritic Ca²⁺ signals were altered in eIF4E-TG SPNs. Together, these findings indicate that eIF4E overexpression biases striatal neurons toward NMDA receptor-dependent LTP.