Sox11 is an Activity-Regulated Gene with Dentate-Gyrus-Specific Expression Upon General Neural Activation

• Published in: Cerebral cortex (New York, N.Y. 1991) N.Y. 1991), 2020-05, Vol.30 (6), p.3731-3743
• Main Authors: von Wittgenstein, Julia, Zheng, Fang, Wittmann, Marie-Theres, Balta, Elli-Anna, Ferrazzi, Fulvia, Schäffner, Iris, Häberle, Benjamin M, Valero-Aracama, Maria J, Koehl, Muriel, Miranda, Carlos J, Kaspar, Brian K, Ekici, Arif B, Reis, André, Abrous, Djoher Nora, Alzheimer, Christian, Lie, D Chichung
• Format: Article
• Language: English
• Subjects: Animals; Dentate Gyrus - metabolism; Electroshock; Exploratory Behavior - physiology; Gene Expression Regulation; Life Sciences; Mice; Mice, Knockout; Neuronal Plasticity - genetics; Neurons - metabolism; Neurons and Cognition; Patch-Clamp Techniques; Proto-Oncogene Proteins c-fos - metabolism; SOXC Transcription Factors - genetics; SOXC Transcription Factors - metabolism
• ISSN: 1047-3211; 1460-2199
• DOI: 10.1093/cercor/bhz338

Abstract Neuronal activity initiates transcriptional programs that shape long-term changes in plasticity. Although neuron subtypes differ in their plasticity response, most activity-dependent transcription factors (TFs) are broadly expressed across neuron subtypes and brain regions. Thus, how region- and neuronal subtype-specific plasticity are established on the transcriptional level remains poorly understood. We report that in young adult (i.e., 6–8 weeks old) mice, the developmental TF SOX11 is induced in neurons within 6 h either by electroconvulsive stimulation or by exploration of a novel environment. Strikingly, SOX11 induction was restricted to the dentate gyrus (DG) of the hippocampus. In the novel environment paradigm, SOX11 was observed in a subset of c-FOS expressing neurons (ca. 15%); whereas around 75% of SOX11+ DG granule neurons were c-FOS+, indicating that SOX11 was induced in an activity-dependent fashion in a subset of neurons. Environmental enrichment or virus-mediated overexpression of SOX11 enhanced the excitability of DG granule cells and downregulated the expression of different potassium channel subunits, whereas conditional Sox11/4 knock-out mice presented the opposite phenotype. We propose that Sox11 is regulated in an activity-dependent fashion, which is specific to the DG, and speculate that activity-dependent Sox11 expression may participate in the modulation of DG neuron plasticity.