Abstract Septin-3 is a neuron-enriched member of the septin family, a group of GTP-binding cytoskeletal proteins. We previously reported that Septin-3 supports late-phase long-term potentiation (L-LTP)–induced entry of smooth endoplasmic reticulum (sER) into dentate gyrus (DG) spines, and that Septin3 −/− mice show reduced numbers of sER-containing DG spines and reduced performance in 24-h novel object recognition. Environmental enrichment (EE) enhances experience-dependent plasticity, raising the possibility that EE could modulate cognitive performance and spine sER phenotypes in Septin3 −/− mice. Here, we tested whether 4-week EE exposure enhances novel object recognition performance in Septin3 −/− mice and whether such behavioral changes are accompanied by changes in the proportion of sER-containing DG spines. Male Septin3 −/− mice were housed in standard housing (SH) or EE for 4 weeks and then subjected to novel object recognition. Septin3 −/− mice exposed to EE showed significantly better performance than SH-housed Septin3 −/− mice in the 24-h test session. Using serial section transmission electron microscopy (ssTEM) and three-dimensional (3D) reconstructions of the DG in Septin3 −/− mice immediately after the novel object recognition test following 4 weeks of SH or EE housing, we found that EE increased synapse density and elevated the proportion of spines containing sER, whereas spine volume and postsynaptic density (PSD) area were not detectably altered. Together, these results show that EE enhances 24-h novel object recognition performance and is associated with an increased proportion of sER-containing DG spines in Septin3 −/− mice following the novel object recognition test.
Ageta‐Ishihara et al. (Thu,) studied this question.