Disruption of Foxg1 impairs neural plasticity leading to social and cognitive behavioral defects

The transcription factor Foxg1 is known to be continuously expressed at a high level in mature neurons in the telencephalon, but little is known about its role in neural plasticity. Mutations in human FOXG1 cause deficiencies in learning and memory and limit social ability, which is defined as FOXG1 syndrome, but its pathogenic mechanism remains unclear. To examine the role of Foxg1 in adults, we crossed Camk2a-Cre^ER with Foxg1^fl/fl mice and conditionally disrupted Foxg1 with tamoxifen in mature neurons. We found that spatial learning and memory were significantly impaired when examined by the Morris water maze test. The cKO mice also showed a significant reduction in freezing time during the contextual and cued fear conditioning test, indicating that fear conditioning memory was affected. A remarkable reduction in Schaffer-collateral long-term potentiation was also recorded. Morphologically, the dendritic arborization and spine densities of hippocampal pyramidal neurons were significantly reduced. Primary cell culture further confirmed altered dendritic complexity after Foxg1 deletion. Our results indicated that Foxg1 plays an important role in maintaining the neural plasticity, which is vital to high-grade function.