Partitioning of lipid-modified monomeric GFPs into membrane microdomains of live cells. Mutual regulation of Src family kinases and the neurotrophin receptor TrkB. TrkB has a cell-autonomous role in the establishment of hippocampal Schaffer collateral synapses. Conditional deletion of TrkB but not BDNF prevents epileptogenesis in the kindling model. A chemical-genetic approach to studying neurotrophin signaling. Sorting and activity-dependent secretion of BDNF require interaction of a specific motif with the sorting receptor carboxypeptidase E. BDNF and its pro-peptide are stored in presynaptic dense core vesicles in brain neurons. Zinc-mediated transactivation of TrkB potentiates the hippocampal mossy fiber-CA3 pyramid synapse. Subunit composition of synaptic AMPA receptors revealed by a single-cell genetic approach. Dual mechanism of a natural CaMKII inhibitor. Identification of TrkB autophosphorylation sites and evidence that phospholipase C-γ1 is a substrate of the TrkB receptor. Rho GTPase complementation underlies BDNF-dependent homo- and heterosynaptic plasticity. Synaptotagmin-IV modulates synaptic function and long-term potentiation by regulating BDNF release. Differential activity-dependent secretion of brain-derived neurotrophic factor from axon and dendrite. Visualizing secretion and synaptic transmission with pH-sensitive green fluorescent proteins. Local, persistent activation of Rho GTPases during plasticity of single dendritic spines. Activation of CaMKII in single dendritic spines during long-term potentiation. The spread of Ras activity triggered by activation of a single dendritic spine. Imaging spatiotemporal dynamics of neuronal signaling using fluorescence resonance energy transfer and fluorescence lifetime imaging microscopy. Loss of Cdc42 leads to defects in synaptic plasticity and remote memory recall. Disruption of Arp2/3 results in asymmetric structural plasticity of dendritic spines and progressive synaptic and behavioral abnormalities. Rapid and persistent modulation of actin dynamics regulates postsynaptic reorganization underlying bidirectional plasticity. Structural basis of long-term potentiation in single dendritic spines. Matsuzaki, M., Honkura, N., Ellis-Davies, G. TrkB phosphorylation by Cdk5 is required for activity-dependent structural plasticity and spatial memory. Protein synthesis and neurotrophin-dependent structural plasticity of single dendritic spines. Postsynaptic induction of BDNF-mediated long-term potentiation. Hippocampal long-term potentiation is impaired in mice lacking brain-derived neurotrophic factor. Regulation of synaptic responses to high-frequency stimulation and LTP by neurotrophins in the hippocampus. Essential role for TrkB receptors in hippocampus-mediated learning. Neurotrophins and time: different roles for TrkB signaling in hippocampal long-term potentiation.
Potentiation of developing neuromuscular synapses by the neurotrophins NT-3 and BDNF.
Together, these findings reveal a spine-autonomous, autocrine signalling mechanism involving NMDAR–CaMKII-dependent BDNF release from stimulated dendritic spines and subsequent TrkB activation on these same spines that is crucial for structural and functional plasticity. We demonstrate that this postsynaptic BDNF–TrkB signalling pathway is necessary for both structural and functional LTP 20. Consistent with these findings, we also show rapid, glutamate-uncaging-evoked, time-locked BDNF release from single dendritic spines using BDNF fused to superecliptic pHluorin 17, 18, 19. We confirm the presence of postsynaptic BDNF using electron microscopy to localize endogenous BDNF to dendrites and spines of hippocampal CA1 pyramidal neurons. In response to sLTP induction 9, 14, 15, 16, we find fast (onset 20 min) activation of TrkB in the stimulated spine that depends on NMDAR ( N-methyl- d-aspartate receptor) and CaMKII signalling and on postsynaptically synthesized BDNF. Here, using a fluorescence resonance energy transfer-based sensor for TrkB and two-photon fluorescence lifetime imaging microscopy 13, 14, 15, 16, we monitor TrkB activity in single dendritic spines of CA1 pyramidal neurons in cultured murine hippocampal slices. However, it is unknown whether BDNF release and TrkB activation occur during sLTP, and if so, when and where. Brain-derived neurotrophic factor (BDNF) and its receptor TrkB are crucial for many forms of neuronal plasticity 1, 2, 3, 4, 5, 6, including structural long-term potentiation (sLTP) 7, 8, which is a correlate of an animal’s learning 7, 9, 10, 11, 12.