PMID- 23587649 OWN - NLM STAT- MEDLINE DCOM- 20140110 LR - 20130524 IS - 1873-7064 (Electronic) IS - 0028-3908 (Linking) VI - 71 DP - 2013 Aug TI - Acute and chronic interference with BDNF/TrkB-signaling impair LTP selectively at mossy fiber synapses in the CA3 region of mouse hippocampus. PG - 247-54 LID - S0028-3908(13)00137-8 [pii] LID - 10.1016/j.neuropharm.2013.03.041 [doi] AB - Brain-derived neurotrophic factor (BDNF) signaling via TrkB crucially regulates synaptic plasticity in the brain. Although BDNF is abundant at hippocampal mossy fiber (MF) synapses, which critically contribute to hippocampus dependent memory, its role in MF synaptic plasticity (long-term potentiation, LTP) remained largely unclear. Using field potential recordings in CA3 of adult heterozygous BDNF knockout (ko, BDNF+/-) mice we observed impaired ( approximately 50%) NMDAR-independent MF-LTP. In contrast to MF synapses, LTP at neighboring associative/commissural (A/C) fiber synapses remained unaffected. To exclude that impaired MF-LTP in BDNF+/- mice was due to developmental changes in response to chronically reduced BDNF levels, and to prove the importance of acute availability of BDNF in MF-LTP, we also tested effects of acute interference with BDNF/TrkB signaling. Inhibition of TrkB tyrosine kinase signaling with k252a, or with the selective BDNF scavenger TrkB-Fc, both inhibited MF-LTP to the same extent as observed in BDNF+/- mice. Basal synaptic transmission, short-term plasticity, and synaptic fatigue during LTP induction were not significantly altered by treatment with k252a or TrkB-Fc, or by chronic BDNF reduction in BDNF+/- mice. Since the acute interference with BDNF-signaling did not completely block MF-LTP, our results provide evidence that an additional mechanism besides BDNF induced TrkB signaling contributes to this type of LTP. Our results prove for the first time a mechanistic action of acute BDNF/TrkB signaling in presynaptic expression of MF-LTP in adult hippocampus. CI - Copyright (c) 2013 Elsevier Ltd. All rights reserved. FAU - Schildt, Sandra AU - Schildt S AD - Institute of Physiology, Medical Faculty, Otto-von-Guericke-University Magdeburg, Germany. FAU - Endres, Thomas AU - Endres T FAU - Lessmann, Volkmar AU - Lessmann V FAU - Edelmann, Elke AU - Edelmann E LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20130412 PL - England TA - Neuropharmacology JT - Neuropharmacology JID - 0236217 RN - 0 (Brain-Derived Neurotrophic Factor) RN - 0 (Nerve Tissue Proteins) RN - 0 (Protein Kinase Inhibitors) RN - EC 2.7.10.1 (Receptor, trkB) SB - IM MH - Animals MH - Brain-Derived Neurotrophic Factor/antagonists & inhibitors/genetics/*metabolism MH - CA3 Region, Hippocampal/drug effects/*metabolism MH - Heterozygote MH - Humans MH - *Long-Term Potentiation/drug effects MH - Male MH - Mice MH - Mice, Inbred C57BL MH - Mice, Knockout MH - Mossy Fibers, Hippocampal/drug effects/*metabolism MH - Nerve Tissue Proteins/antagonists & inhibitors/genetics/metabolism MH - Neural Inhibition/drug effects MH - Presynaptic Terminals/drug effects/metabolism MH - Protein Kinase Inhibitors/pharmacology MH - Receptor, trkB/antagonists & inhibitors/*metabolism MH - *Signal Transduction/drug effects MH - Synapses/drug effects/*metabolism MH - Synaptic Transmission/drug effects MH - Time Factors EDAT- 2013/04/17 06:00 MHDA- 2014/01/11 06:00 CRDT- 2013/04/17 06:00 PHST- 2012/12/09 00:00 [received] PHST- 2013/02/27 00:00 [revised] PHST- 2013/03/01 00:00 [accepted] PHST- 2013/04/17 06:00 [entrez] PHST- 2013/04/17 06:00 [pubmed] PHST- 2014/01/11 06:00 [medline] AID - S0028-3908(13)00137-8 [pii] AID - 10.1016/j.neuropharm.2013.03.041 [doi] PST - ppublish SO - Neuropharmacology. 2013 Aug;71:247-54. doi: 10.1016/j.neuropharm.2013.03.041. Epub 2013 Apr 12.