PMID- 18639615 OWN - NLM STAT- MEDLINE DCOM- 20081218 LR - 20211020 IS - 0306-4522 (Print) IS - 0306-4522 (Linking) VI - 155 IP - 3 DP - 2008 Aug 26 TI - Coordinate action of pre- and postsynaptic brain-derived neurotrophic factor is required for AMPAR trafficking and acquisition of in vitro classical conditioning. PG - 686-97 LID - 10.1016/j.neuroscience.2008.06.043 [doi] AB - Brain-derived neurotrophic factor (BDNF) has been implicated in mechanisms of synaptic plasticity such as long-term potentiation (LTP), but its role in associative learning remains largely unknown. In the present study, we investigated the function of BDNF and its receptor tropomyosin-related kinase B (TrkB) in an in vitro model of classical conditioning using pond turtles, Pseudemys scripta elegans. Conditioning resulted in a significant increase in BDNF and phospho (p)-Trk expression. Bath application of antibodies directed against TrkB, but not TrkA or TrkC, abolished acquisition of conditioning, as did a receptor tyrosine kinase inhibitor K252a and an inhibitor of nitric oxide synthase 7-nitroindazole. Significantly, injections of BDNF Ab into the nerve roots of presynaptic axonal projections or postsynaptic motor neurons prevented acquisition of conditioning, suggesting that BDNF is required on both sides of the synapse for modification to occur. The presynaptic proteins synaptophysin and synapsin I were increased upon conditioning or BDNF application. Furthermore, BDNF application alone mimicked conditioning-induced synaptic insertion of GluR1 and GluR4 AMPAR subunits into synapses, which was inhibited by co-application of BDNF and K252a. Data also show that extracellular signal-regulated kinase (ERK) was activated in BDNF-treated preparations. We conclude that coordinate pre- and postsynaptic actions of BDNF are required for acquisition of in vitro classical conditioning. FAU - Li, W AU - Li W AD - Neuroscience Group, Division of Basic Biomedical Sciences, University of South Dakota School of Medicine, 414 East Clark Street, Vermillion, SD 57069, USA. FAU - Keifer, J AU - Keifer J LA - eng GR - P20 RR-015567/RR/NCRR NIH HHS/United States GR - P20 RR015567-09/RR/NCRR NIH HHS/United States GR - P20 RR015567/RR/NCRR NIH HHS/United States GR - R01 NS051187-08/NS/NINDS NIH HHS/United States GR - R01 NS051187-09/NS/NINDS NIH HHS/United States GR - P20 RR015567-08/RR/NCRR NIH HHS/United States GR - NS-051187/NS/NINDS NIH HHS/United States GR - R01 NS051187/NS/NINDS NIH HHS/United States PT - Journal Article PT - Research Support, N.I.H., Extramural DEP - 20080625 PL - United States TA - Neuroscience JT - Neuroscience JID - 7605074 RN - 0 (Antibodies) RN - 0 (Brain-Derived Neurotrophic Factor) RN - 0 (Enzyme Inhibitors) RN - 0 (Receptors, AMPA) RN - 452VLY9402 (Serine) RN - EC 2.7.10.1 (Receptor, trkA) RN - EC 2.7.11.24 (Extracellular Signal-Regulated MAP Kinases) SB - IM MH - Animals MH - Antibodies/pharmacology MH - Brain Stem/cytology/physiology MH - Brain-Derived Neurotrophic Factor/immunology/*metabolism MH - Cochlear Nerve/physiology MH - Conditioning, Classical/*drug effects/physiology MH - Enzyme Inhibitors/pharmacology MH - Extracellular Signal-Regulated MAP Kinases/metabolism MH - Gene Expression Regulation/drug effects/physiology MH - In Vitro Techniques MH - Motor Neurons/cytology/drug effects/physiology MH - Neural Pathways/drug effects/metabolism MH - Phosphorylation MH - Physical Stimulation/methods MH - Protein Transport/drug effects MH - Receptor, trkA/metabolism MH - Receptors, AMPA/*metabolism MH - Serine/metabolism MH - Synapses/*drug effects MH - Time Factors MH - Turtles PMC - PMC2607041 MID - NIHMS68807 EDAT- 2008/07/22 09:00 MHDA- 2008/12/19 09:00 PMCR- 2009/08/26 CRDT- 2008/07/22 09:00 PHST- 2008/04/03 00:00 [received] PHST- 2008/05/23 00:00 [revised] PHST- 2008/06/11 00:00 [accepted] PHST- 2008/07/22 09:00 [pubmed] PHST- 2008/12/19 09:00 [medline] PHST- 2008/07/22 09:00 [entrez] PHST- 2009/08/26 00:00 [pmc-release] AID - S0306-4522(08)00901-9 [pii] AID - 10.1016/j.neuroscience.2008.06.043 [doi] PST - ppublish SO - Neuroscience. 2008 Aug 26;155(3):686-97. doi: 10.1016/j.neuroscience.2008.06.043. Epub 2008 Jun 25.