title: BDNF and Hippocampal Synaptic Plasticity.
abstract: Brain-derived neurotrophic factor (BDNF) belongs to a family of small secreted proteins that also include nerve growth factor, neurotrophin 3, and neurotrophin 4. BDNF stands out among all neurotrophins by its high expression levels in the brain and its potent effects at synapses. Several aspects of BDNF biology such as transcription, processing, and secretion are regulated by synaptic activity. Such observations prompted the suggestion that BDNF may regulate activity-dependent forms of synaptic plasticity such as long-term potentiation (LTP), a sustained enhancement of excitatory synaptic efficacy thought to underlie learning and memory. Here, we will review the evidence pointing to a fundamental role of this neurotrophin in LTP, especially within the hippocampus. Prominent questions in the field, including the release and action sites of BDNF during LTP, as well as the signaling and molecular mechanisms involved, will also be addressed. The diverse effects of BDNF at excitatory synapses are determined by the activation of TrkB receptors and downstream signaling pathways, and the functions, typically opposing in nature, of its immature form (proBDNF). The activation of p75NTRreceptors by proBDNF and the implications for long-term depression will also be addressed. Finally, we discuss the synergy between TrkB and glucocorticoid receptor signaling to determine cellular responses to stress.
authors.affiliation: CNC-Center for Neuroscience and Cell Biology, University of Coimbra, Coimbra, Portugal.
authors.forename: G
authors.initials: G
authors.lastname: Leal
authors.affiliation: K.G. Jebsen Center for Neuropsychiatric Disorders, University of Bergen, Bergen, Norway.
authors.forename: C R
authors.initials: CR
authors.lastname: Bramham
authors.affiliation: CNC-Center for Neuroscience and Cell Biology, University of Coimbra, Coimbra, Portugal; University of Coimbra, Coimbra, Portugal. Electronic address: cbduarte@ci.uc.pt.
authors.forename: C B
authors.initials: CB
authors.lastname: Duarte
mesh_terms: D000818:Animals; D019208:Brain-Derived Neurotrophic Factor / Q000235:genetics / Q000378:metabolism*; D018507:Gene Expression Regulation, Developmental; D006624:Hippocampus / Q000166:cytology / Q000378:metabolism*; D006801:Humans; D017774:Long-Term Potentiation; D008959:Models, Neurological; D055495:Neurogenesis; D009473:Neuronal Plasticity; D009474:Neurons / Q000166:cytology / Q000378:metabolism*; D020800:Receptor, Nerve Growth Factor / Q000819:agonists / Q000378:metabolism; D047889:Receptors, Tumor Necrosis Factor, Type II / Q000819:agonists / Q000378:metabolism; D015398:Signal Transduction
chemical_list: D019208:Brain-Derived Neurotrophic Factor; D020800:Receptor, Nerve Growth Factor; D047889:Receptors, Tumor Necrosis Factor, Type II; C415902:TNFRSF1B protein, human; C579455:BDNF protein, human
keywords: BDNF; Hippocampus; LTP; Synaptic plasticity; TrkB