title: Activity-dependent modulation of the BDNF receptor TrkB: mechanisms and implications.
abstract: Although brain-derived neurotrophic factor (BDNF) has emerged as a key regulator of activity-dependent synaptic plasticity, a conceptually challenging question is how this diffusible molecule achieves local and synapse-specific modulation. One hypothesis is that neuronal activity enhances BDNF signaling by selectively modulating TrkB receptors at active neurons or synapses without affecting receptors on neighboring, less-active ones. Growing evidence suggests that neuronal activity facilitates cell-surface expression of TrkB. BDNF secreted from active synapses and neurons recruits TrkB from extrasynaptic sites into lipid rafts, microdomains of membrane that are enriched at synapses. Postsynaptic rises in cAMP concentrations facilitate translocation of TrkB into the postsynaptic density. Finally, neuronal activity promotes BDNF-induced TrkB endocytosis, a signaling event important for many long-term BDNF functions. These mechanisms could collectively underlie synapse-specific regulation by BDNF.
authors.affiliation: Section on Neural Development and Plasticity, National Institute of Child Health and Human Development, National Institutes of Health, 35 Lincoln Drive, MSC 3714, Bethesda, MD 20892-4480, USA.
authors.forename: Guhan
authors.initials: G
authors.lastname: Nagappan
authors.forename: Bai
authors.initials: B
authors.lastname: Lu
mesh_terms: D000818:Animals; D001921:Brain / Q000502:physiology*; D019208:Brain-Derived Neurotrophic Factor / Q000378:metabolism; D006801:Humans; D009473:Neuronal Plasticity / Q000502:physiology*; D009474:Neurons / Q000378:metabolism; D021381:Protein Transport / Q000502:physiology*; D020813:Receptor, trkB / Q000378:metabolism*; D013569:Synapses / Q000378:metabolism*
chemical_list: D019208:Brain-Derived Neurotrophic Factor; D020813:Receptor, trkB