The ever-changing brain: cellular and molecular mechanisms for the effects of stressful experiences

The adult brain is capable of considerable structural and functional plasticity and the study of hormone actions in brain has contributed to our understanding of this important phenomenon. In particular, stress and stress-related hormones such as glucocorticoids and mineralocorticoids play a key role in the ability of acute and chronic stress to cause reversible remodeling of neuronal connections in the hippocampus, prefrontal cortex, and amygdala. To produce this plasticity, these hormones act by both genomic and non-genomic mechanisms together with ongoing, experience-driven neural activity mediated by excitatory amino acid neurotransmitters, neurotrophic factors such as brain derived neurotrophic factor, extracellular molecules such as neural cell adhesion molecule, neuropeptides such as corticotrophin releasing factor, and endocannabinoids. The result is a dynamic brain architecture that can be modified by experience. Under this view, the role of pharmaceutical agents, such as antidepressants, is to facilitate such plasticity that must also be guided by experiences.