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bioRxiv · 10.64898/2026.05.26.727726

Effects of Glutamate Delta 1 Receptor (GluD1) Deletion on the Ultrastructural Features of Corticostriatal and Thalamostriatal Synapses in Mice

Yue, L.·Dalal, K.·Dravid, S. M.·Smith, Y.·Villalba, R. M.
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Abstract

The glutamate delta 1 receptor (GluD1) represents a unique subtype of ionotropic glutamate receptors that is strongly expressed in the mammalian striatum. Disruptions of the GRID1 gene, which encodes GluD1, have been associated with neuropsychiatric disorders, including schizophrenia and autism spectrum disorder; however, the role of GluD1 in the brain remains poorly understood. Previous studies in mice have demonstrated that the knockout of striatal GluD1 led to fear-conditioning deficits and depressive-like behaviors. Furthermore, these mice exhibited reduced excitatory input to the striatum due to a loss of thalamostriatal innervation, whereas corticostriatal innervation was unaffected. In this study, we examined whether changes in synapse morphology contribute to the observed functional deficits. We found that the ablation of GluD1 does not affect synaptic targeting patterns of corticostriatal and thalamostriatal terminals, using transmission electron microscopy. We further utilized three-dimensional reconstruction to obtain quantitative data on synapse ultrastructure and found no significant changes in corticostriatal and thalamostriatal synaptic components, including the presynaptic terminal volume, postsynaptic density area and morphology, and postsynaptic dendritic spine volume. These findings support a model in which GluD1 regulates input-specific circuit organization and synaptic connectivity rather than the structural morphology of individual synapses.

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Yue, L., Dalal, K., Dravid, S. M., Smith, Y., Villalba, R. M.. 2026-05-28. Effects of Glutamate Delta 1 Receptor (GluD1) Deletion on the Ultrastructural Features of Corticostriatal and Thalamostriatal Synapses in Mice. https://doi.org/10.64898/2026.05.26.727726

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