title: Mice lacking the gene encoding tissue-type plasminogen activator show a selective interference with late-phase long-term potentiation in both Schaffer collateral and mossy fiber pathways.
abstract: The gene encoding tissue-type plasminogen activator (t-PA) is an immediate response gene, downstream from CREB-1 and other constitutively expressed transcription factors, which is induced in the hippocampus during the late phase of long-term potentiation (L-LTP). Mice in which the t-PA gene has been ablated (t-PA-/-) showed no gross anatomical, electrophysiological, sensory, or motor abnormalities but manifest a selective reduction in L-LTP in hippocampal slices in both the Schaffer collateral-CA1 and mossy fiber-CA3 pathways. t-PA-/- mice also exhibit reduced potentiation by cAMP analogs and D1/D5 agonists. By contrast, hippocampal-dependent learning and memory were not affected in these mice, whereas performance was impaired on two-way active avoidance, a striatum-dependent task. These results provide genetic evidence that t-PA is a downstream effector gene important for L-LTP and show that modest impairment of L-LTP in CA1 and CA3 does not result in hippocampus-dependent behavioral phenotypes.
authors.affiliation: Howard Hughes Medical Institute, Center for Neurobiology and Behavior, College of Physicians and Surgeons of Columbia University, New York, USA.
authors.forename: Y Y
authors.initials: YY
authors.lastname: Huang
authors.forename: M E
authors.initials: ME
authors.lastname: Bach
authors.forename: H P
authors.initials: HP
authors.lastname: Lipp
authors.forename: M
authors.initials: M
authors.lastname: Zhuo
authors.forename: D P
authors.initials: DP
authors.lastname: Wolfer
authors.forename: R D
authors.initials: RD
authors.lastname: Hawkins
authors.forename: L
authors.initials: L
authors.lastname: Schoonjans
authors.forename: E R
authors.initials: ER
authors.lastname: Kandel
authors.forename: J M
authors.initials: JM
authors.lastname: Godfraind
authors.forename: R
authors.initials: R
authors.lastname: Mulligan
authors.forename: D
authors.initials: D
authors.lastname: Collen
authors.forename: P
authors.initials: P
authors.lastname: Carmeliet
mesh_terms: D000818:Animals; D001362:Avoidance Learning / Q000502:physiology; D001522:Behavior, Animal / Q000502:physiology; D003213:Conditioning, Psychological / Q000502:physiology; D006624:Hippocampus / Q000502:physiology*; D066298:In Vitro Techniques; D017774:Long-Term Potentiation / Q000502:physiology*; D008568:Memory / Q000502:physiology*; D051379:Mice; D018345:Mice, Knockout; D009434:Neural Pathways / Q000502:physiology; D009473:Neuronal Plasticity / Q000502:physiology; D013028:Space Perception / Q000502:physiology; D010959:Tissue Plasminogen Activator / Q000172:deficiency / Q000502:physiology*
chemical_list: D010959:Tissue Plasminogen Activator