Mechanisms of homeostatic plasticity in the excitatory synapse

Brain development, sensory information processing, and learning and memory processes depend on Hebbian forms of synaptic plasticity, and on the remodeling and pruning of synaptic connections. Neurons in networks implicated in these processes carry out their functions while facing constant perturbation; homeostatic responses are therefore required to maintain neuronal activity within functional ranges for proper brain function. Here, we will review in vitro and in vivo studies demonstrating that several mechanisms underlie homeostatic plasticity of excitatory synapses, and identifying participant molecular players. Emerging evidence suggests a link between disrupted homeostatic synaptic plasticity and neuropsychiatric and neurologic disorders. Hebbian forms of synaptic plasticity, such as long-term potentiation (LTP), induce long-lasting changes in synaptic strength, which can be destabilizing and drive activity to saturation. Conversely, homeostatic plasticity operates to compensate for prolonged activity changes, stabilizing neuronal firing within a dynamic physiological range. We review mechanisms underlying homeostatic plasticity, and address how neurons integrate distinct forms of plasticity for proper brain function. This article is part of a mini review series: "Synaptic Function and Dysfunction in Brain Diseases".