title: Blockade of BDNF signaling turns chemically-induced long-term potentiation into long-term depression.
abstract: Long-term potentiation (LTP) is accompanied by increased spine density and dimensions triggered by signaling cascades involving activation of the neurotrophin brain-derived neurotrophic factor (BDNF) and cytoskeleton remodeling. Chemically-induced long-term potentiation (c-LTP) is a widely used cellular model of plasticity, whose effects on spines have been poorly investigated. We induced c-LTP by bath-application of the N-methyl-d-aspartate receptor (NMDAR) coagonist glycine or by the K(+) channel blocker tetraethylammonium (TEA) chloride in cultured hippocampal neurons and compared the changes in dendritic spines induced by the two models of c-LTP and determined if they depend on BDNF/TrkB signaling. We found that both TEA and glycine induced a significant increase in stubby spine density in primary and secondary apical dendrites, whereas a specific increase in mushroom spine density was observed upon TEA application only in primary dendrites. Both TEA and glycine increased BDNF levels and the blockade of tropomyosin-receptor-kinase receptors (TrkRs) by the nonselective tyrosine kinase inhibitor K-252a or the selective allosteric TrkB receptor (TrkBR) inhibitor ANA-12, abolished the c-LTP-induced increase in spine density. Surprisingly, a blockade of TrkBRs did not change basal spontaneous glutamatergic transmission but completely changed the synaptic plasticity induced by c-LTP, provoking a shift from a long-term increase to a long-term depression (LTD) in miniature excitatory postsynaptic current (mEPSC) frequency. In conclusion, these results suggest that BDNF/TrkB signaling is necessary for c-LTP-induced plasticity in hippocampal neurons and its blockade leads to a switch of c-LTP into chemical-LTD (c-LTD).
authors.affiliation: Department of Life Sciences and B.R.A.I.N., Centre for Neuroscience, University of Trieste, Trieste, Italy.
authors.forename: A
authors.initials: A
authors.lastname: Montalbano
authors.forename: G
authors.initials: G
authors.lastname: Baj
authors.forename: D
authors.initials: D
authors.lastname: Papadia
authors.forename: E
authors.initials: E
authors.lastname: Tongiorgi
authors.forename: M
authors.initials: M
authors.lastname: Sciancalepore
mesh_terms: D000818:Animals; D019208:Brain-Derived Neurotrophic Factor / Q000037:antagonists & inhibitors / Q000378:metabolism*; D002478:Cells, Cultured; D049229:Dendritic Spines / Q000187:drug effects / Q000502:physiology*; D019706:Excitatory Postsynaptic Potentials / Q000187:drug effects; D005998:Glycine / Q000494:pharmacology; D018684:Glycine Agents / Q000494:pharmacology; D006624:Hippocampus / Q000166:cytology / Q000378:metabolism*; D017774:Long-Term Potentiation / Q000187:drug effects / Q000502:physiology*; D036881:Long-Term Synaptic Depression / Q000187:drug effects / Q000502:physiology*; D018408:Patch-Clamp Techniques; D026902:Potassium Channel Blockers / Q000494:pharmacology; D017208:Rats, Wistar; D020813:Receptor, trkB / Q000037:antagonists & inhibitors / Q000378:metabolism*; D016194:Receptors, N-Methyl-D-Aspartate / Q000819:agonists; D015398:Signal Transduction / Q000187:drug effects / Q000502:physiology*; D019789:Tetraethylammonium / Q000494:pharmacology
chemical_list: D019208:Brain-Derived Neurotrophic Factor; D018684:Glycine Agents; D026902:Potassium Channel Blockers; D016194:Receptors, N-Methyl-D-Aspartate; D019789:Tetraethylammonium; D020813:Receptor, trkB; D005998:Glycine
keywords: TEA; glycine; chemical LTD; chemical LTP; spine remodeling