MARCKSL1 regulates spine formation and controls anxiety

Abnormalities in the limbic neural circuits have been implicated in the onset of anxiety disorders. However, the molecular pathogenesis underlying anxiety disorders remains poorly elucidated. Here, we demonstrate that myristoylated alanine-rich C-kinase substrate like 1 (MARCKSL1) regulates the amygdala circuitry to control the activity of hypothalamic-pituitary-adrenal (HPA) axis and induces anxiety behaviors in mice. MARCKSL1 expression was predominantly localized in the prefrontal cortex (PFC), hypothalamus, hippocampus, and amygdala of the adult mouse brain. MARCKSL1 transgenic (Tg) mice exhibited anxiety-like behaviors dependent on corticotropin releasing hormone. MARCKSL1 increased the spine formation in the central amygdala, and the downregulation of MARCKSL1 in the amygdala normalized both increased activity of the HPA axis and elevated anxiety-like behaviors in Tg mice. Furthermore, there was increased MARCKSL1 expression in the PFC and amygdala in a brain injury model associated with anxiety-like behaviors. Our findings suggest that MARCKSL1 expression in the amygdala plays an important role in anxiety-related behaviors.