The stressed cytoskeleton: How actin dynamics can shape stress-related consequences on synaptic plasticity and complex behavior

Stress alters synaptic plasticity but the molecular and cellular mechanisms through which environmental stimuli modulate synaptic function remain to be elucidated. Actin filaments are the major structural component of synapses and their rearrangements by actin-binding proteins (ABPs) are critical for fine-tuning synaptic plasticity. Accumulating evidence suggests that some ABPs are specifically regulated by stress and stress-related effectors such as glucocorticoids and corticotropin releasing hormone. ABPs may thus be central in stress-induced perturbations at the level of synaptic plasticity, leading to impairments in behavioral domains including cognitive performance and social behavior. Identified stress-responsive ABPs include: tumor suppressor down-regulated in renal cell carcinoma 1 (DRR1), ADF/cofilin, LIMK1, caldesmon and myosin VI. Here we discuss how stress may impact synaptic plasticity through specific effects on these ABPs and how these adaptations might modulate complex behavior, predisposing individuals at genetic risk for the development of mental dysfunctions. We argue that a precise understanding of the mechanisms underlying stress-associated changes in synaptic function could stimulate the development of innovative treatment strategies against stress-related mental disorders.