Environmental Enrichment and Social Isolation Mediate Neuroplasticity of Medium Spiny Neurons through the GSK3 Pathway

• DOI: 10.1016/j.celrep.2018.03.062
• Publication Date: 2018-04-10T15:45:38Z
• Authors: Federico Scala; Miroslav N. Nenov; Elizabeth J. Crofton; Aditya K. Singh; Oluwarotimi Folor...; Yafang Zhang; Brent C. Chesson; Norelle C. Wildbu...; Thomas F. James; Musaad A. Alshammari; Tahani K. Alshammari; Hannah Elfrink; Claudio Grassi; James M. Kasper; Ashley E. Smith; Jonathan D. Hommel; Cheryl F. Lichti; Jai S. Rudra; Marcello D’Ascenzo; Thomas A. Green; Fernanda Laezza
• Keywords: Environmental Enrichment; Medium spiny neuron; Isolation; Social Isolation

Resilience and vulnerability to neuropsychiatric disorders are linked molecular changes underlying excitability that still poorly understood. Here, we identify glycogen-synthase kinase 3β (GSK3β) voltage-gated Na+ channel Nav1.6 as regulators of neuroplasticity induced by environmentally enriched (EC) or isolated (IC) conditions-models for resilience vulnerability. Transcriptomic studies in the nucleus accumbens from EC IC rats predicted low levels GSK3β SCN8A mRNA a protective phenotype associated with reduced medium spiny neurons (MSNs). In vivo genetic manipulations demonstrate determinants MSN silencing prevents maladaptive plasticity MSNs. vitro reveal direct interaction phosphorylation at Nav1.6T1936 GSK3β. A GSK3β-Nav1.6T1936 competing peptide reduces MSNs IC, but not rats. These results regulation biosignature plasticity.