title: Essential role of presynaptic NMDA receptors in activity-dependent BDNF secretion and corticostriatal LTP.
abstract: Activation of N-methyl-D-aspartate subtype of glutamate receptors (NMDARs) in postsynaptic dendrites is required for long-term potentiation (LTP) of many excitatory synapses, but the role of presynaptic axonal NMDARs in synaptic plasticity remains to be clarified. Here we report that axonal NMDARs play an essential role in LTP induction at mouse corticostriatal synapses by triggering activity-induced presynaptic secretion of brain-derived neurotrophic factor (BDNF). Genetic depletion of either BDNF or the NMDAR subunit GluN1 specifically in cortical axons abolished corticostriatal LTP in response to theta burst stimulation (TBS). Furthermore, functional axonal NMDARs were required for TBS-triggered prolonged axonal Ca(2+) elevation and BDNF secretion, supporting the notion that activation of axonal NMDARs induces BDNF secretion via enhancing Ca(2+) signals in the presynaptic nerve terminals. These results demonstrate that presynaptic NMDARs are equally important as postsynaptic NMDARs in LTP induction of corticostriatal synapses due to their role in mediating activity-induced presynaptic BDNF secretion.
authors.affiliation: Division of Neurobiology, Department of Molecular and Cell Biology, Helen Wills Neuroscience Institute, University of California, Berkeley, CA 94720.
authors.forename: Hyungju
authors.initials: H
authors.lastname: Park
authors.affiliation: Division of Neurobiology, Department of Molecular and Cell Biology, Helen Wills Neuroscience Institute, University of California, Berkeley, CA 94720.
authors.forename: Andrei
authors.initials: A
authors.lastname: Popescu
authors.affiliation: Division of Neurobiology, Department of Molecular and Cell Biology, Helen Wills Neuroscience Institute, University of California, Berkeley, CA 94720; Institute of Neuroscience, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Shanghai 200031, China. Electronic address: mpoo@berkeley.edu.
authors.forename: Mu-ming
authors.initials: MM
authors.lastname: Poo
mesh_terms: D000818:Animals; D000906:Antibodies / Q000494:pharmacology; D019208:Brain-Derived Neurotrophic Factor / Q000235:genetics / Q000378:metabolism*; D054732:Calcium-Calmodulin-Dependent Protein Kinase Type 2 / Q000235:genetics; D002540:Cerebral Cortex / Q000166:cytology*; D003342:Corpus Striatum / Q000166:cytology*; D018691:Excitatory Amino Acid Antagonists / Q000494:pharmacology; D017774:Long-Term Potentiation / Q000187:drug effects / Q000235:genetics / Q000502:physiology*; D008164:Luminescent Proteins / Q000235:genetics / Q000378:metabolism; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D018613:Microscopy, Confocal; D008954:Models, Biological; D009474:Neurons / Q000187:drug effects / Q000502:physiology*; D020813:Receptor, trkB / Q000276:immunology; D016194:Receptors, N-Methyl-D-Aspartate / Q000378:metabolism*; D013569:Synapses / Q000235:genetics / Q000502:physiology*; D013997:Time Factors; D014633:Valine / Q000031:analogs & derivatives / Q000494:pharmacology
chemical_list: D000906:Antibodies; D019208:Brain-Derived Neurotrophic Factor; D018691:Excitatory Amino Acid Antagonists; D008164:Luminescent Proteins; D016194:Receptors, N-Methyl-D-Aspartate; C056639:2-amino-5-phosphopentanoic acid; D020813:Receptor, trkB; D054732:Calcium-Calmodulin-Dependent Protein Kinase Type 2; D014633:Valine