title: The expression mechanism of the residual LTP in the CA1 region of BDNF k.o. mice is insensitive to NO synthase inhibition.
abstract: BDNF and nitric oxide signaling both contribute to long-term potentiation (LTP) at glutamatergic synapses, but to date, few studies analyzed the interaction of both signaling cascades in the same synaptic pathway. Here we addressed the question whether the residual LTP in the CA1 region of hippocampal slices from heterozygous BDNF knockout mice (BDNF⁺/⁻) is dependent on nitric oxide (NO) signaling. Extracellular recording of synaptic field potentials elicited by presynaptic Schaffer collateral stimulation was performed in the CA1 region of hippocampal slices of 4- to 6-week-old mice, and LTP was induced by a theta burst stimulation protocol. Application of the nitric oxide inhibitor L-NAME (200 μM) strongly inhibited LTP by 70% in wildtype animals. This inhibition of LTP was not a consequence of altered basal synaptic properties. In CA1 of BDNF⁺/⁻ mice, stimulated with the same theta burst protocol, LTP was reduced by 50% as compared to wildtype animals. This impairment in the expression of LTP in BDNF⁺/⁻ mice did not result from an increased synaptic fatigue. The residual LTP in BDNF⁺/⁻ was not further reduced by preincubation of slices with L-NAME. These results suggest that BDNF and NO share overlapping intracellular signaling cascades to mediate LTP in CA1, and part of their signaling cascades are most likely arranged consecutively in the signaling pathway mediating LTP.
authors: Institute of Physiology and Pathophysiology, University Medical Center Mainz, Johannes Gutenberg-University, Mainz, Germany. lessmann@med.ovgu.de
authors: Volkmar
authors: V
authors: Lessmann
authors: Sigrid
authors: S
authors: Stroh-Kaffei
authors: Violetta
authors: V
authors: Steinbrecher
authors: Elke
authors: E
authors: Edelmann
authors: Tanja
authors: T
authors: Brigadski
authors: Werner
authors: W
authors: Kilb
authors: Heiko J
authors: HJ
authors: Luhmann
mesh_terms: D000818:Animals; D000831:Animals, Newborn; D001703:Biophysics; D019208:Brain-Derived Neurotrophic Factor / Q000172:deficiency*; D056547:CA1 Region, Hippocampal / Q000166:cytology*; D004558:Electric Stimulation / Q000379:methods; D004791:Enzyme Inhibitors / Q000494:pharmacology; D019706:Excitatory Postsynaptic Potentials / Q000187:drug effects / Q000235:genetics; D066298:In Vitro Techniques; D017774:Long-Term Potentiation / Q000187:drug effects / Q000235:genetics*; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D019331:NG-Nitroarginine Methyl Ester / Q000494:pharmacology; D019001:Nitric Oxide Synthase / Q000378:metabolism*
chemical_list: D019208:Brain-Derived Neurotrophic Factor; D004791:Enzyme Inhibitors; D019001:Nitric Oxide Synthase; D019331:NG-Nitroarginine Methyl Ester