title: A protein synthesis and nitric oxide-dependent presynaptic enhancement in persistent forms of long-term potentiation.
abstract: Long-term potentiation (LTP) is an important process underlying learning and memory in the brain. At CA3-CA1 synapses in the hippocampus, three discrete forms of LTP (LTP1, 2, and 3) can be differentiated on the basis of maintenance and induction mechanisms. However, the relative roles of pre- and post-synaptic expression mechanisms in LTP1, 2, and 3 are unknown. Neurotransmitter release in the expression of LTP1, 2, and 3 was measured via FM 1-43 destaining from CA3 terminals in hippocampal slices from male Wistar rats (7-8 wk). No difference in vesicle turnover rate was observed for LTP1 up to 160 min following induction by one train of theta-burst stimulation (1TBS). A presynaptic enhancement was found for LTP2 at 160 min after induction by 4TBS, and for LTP3 at both 80 and 160 min after induction by 8TBS. Inhibition of nitric oxide (NO) signaling blocked both LTP2 and LTP3 maintenance and the associated enhanced release. LTP2 maintenance and its presynaptic expression were dependent on protein synthesis, but not gene transcription. LTP3 maintenance was dependent on both translation and transcription, but like LTP2, the enhanced release only required translation. These data considerably strengthen the mechanistic separation of LTP1, 2, and 3, supporting a model of multiple, discrete forms of LTP at CA3-CA1 synapses rather than different temporal phases.
authors.affiliation: Department of Neuroscience, The John Curtin School of Medical Research & Eccles Institute of Neuroscience, The Australian National University, Canberra ACT 0200, Australia.
authors.forename: Victoria P A
authors.initials: VP
authors.lastname: Johnstone
authors.forename: Clarke R
authors.initials: CR
authors.lastname: Raymond
mesh_terms: D000818:Animals; D056547:CA1 Region, Hippocampal / Q000502:physiology; D056654:CA3 Region, Hippocampal / Q000502:physiology; D003497:Cyclic N-Oxides / Q000494:pharmacology; D004558:Electric Stimulation; D055724:Electrophysiological Phenomena; D004791:Enzyme Inhibitors / Q000494:pharmacology; D019706:Excitatory Postsynaptic Potentials / Q000502:physiology; D016166:Free Radical Scavengers / Q000494:pharmacology; D006624:Hippocampus / Q000502:physiology; D007093:Imidazoles / Q000494:pharmacology; D066298:In Vitro Techniques; D007700:Kinetics; D017774:Long-Term Potentiation / Q000187:drug effects / Q000502:physiology*; D008297:Male; D008856:Microscopy, Fluorescence; D019331:NG-Nitroarginine Methyl Ester / Q000494:pharmacology; D009419:Nerve Tissue Proteins / Q000096:biosynthesis*; D009569:Nitric Oxide / Q000502:physiology*; D019001:Nitric Oxide Synthase / Q000037:antagonists & inhibitors; D017729:Presynaptic Terminals / Q000187:drug effects / Q000502:physiology*; D011500:Protein Synthesis Inhibitors / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar; D015398:Signal Transduction / Q000187:drug effects / Q000502:physiology; D009435:Synaptic Transmission
chemical_list: D003497:Cyclic N-Oxides; D004791:Enzyme Inhibitors; D016166:Free Radical Scavengers; D007093:Imidazoles; D009419:Nerve Tissue Proteins; D011500:Protein Synthesis Inhibitors; C079391:2-phenyl-4,4,5,5-tetramethylimidazoline-1-oxyl-3-oxide; D009569:Nitric Oxide; D019001:Nitric Oxide Synthase; D019331:NG-Nitroarginine Methyl Ester