- eIF4E overexpression increases dendritic spine density and raises AMPA and NMDA mEPSC frequency while reducing AMPA mEPSC amplitude.
- Striatal spiny projection neurons exhibit enhanced NMDA receptor-dependent LTP induction and magnitude, unchanged by D1 or D2 receptor antagonism.
- Depolarisation-evoked somatic and dendritic Ca2+ signals are altered, biasing striatal neurons towards NMDA receptor-dependent LTP.
iScience. 2026 Sep 3;29(9):117278. doi: 10.1016/j.isci.2026.117278. eCollection 2026 Sep 18.
ABSTRACT
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.
PMID:42733661 | PMC:PMC13571666 | DOI:10.1016/j.isci.2026.117278
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