BDNF signaling in context: From synaptic regulation to psychiatric disorders

Brain-derived neurotrophic factor (BDNF) is a neuropeptide that plays numerous important roles in synaptic development and plasticity. While its importance in fundamental physiology is well established, studies of BDNF often produce conflicting and unclear results, and the scope of existing research makes the prospect of setting future directions daunting. In this review, we examine the importance of spatial and temporal factors on BDNF activity, particularly in processes such as synaptogenesis, Hebbian plasticity, homeostatic plasticity, and the treatment of psychiatric disorders. Understanding the fundamental physiology of when, where, and how BDNF acts and new approaches to control BDNF signaling in time and space can contribute to improved therapeutics and patient outcomes. The pleiotropic and sometimes apparently contradictory functions of brain-derived neurotrophic factor (BDNF) can be resolved through the lens of context. Implications for the development of improved neuropsychiatric treatment and patient outcomes ensue.