title: Foreground contextual fear memory consolidation requires two independent phases of hippocampal ERK/CREB activation.
abstract: Fear conditioning is a popular model for investigating physiological and cellular mechanisms of memory formation. In this paradigm, a footshock is either systematically associated to a tone (paired conditioning) or is pseudorandomly distributed (unpaired conditioning). In the former procedure, the tone/shock association is acquired, whereas in the latter procedure, the context/shock association will prevail. Animals with chronically implanted recording electrodes show enhanced amplitude of the extracellularly recorded field EPSP in CA1 pyramidal cells for up to 24 h after unpaired, but not paired, fear conditioning. This is paralleled by a differential activation of the ERK/CREB pathway in CA1, which is monophasic in paired conditioning (0-15 min post-conditioning), but biphasic (0-1 h and 9-12 h post-conditioning) in unpaired conditioning as revealed by immunocytochemistry and Western blotting. Intrahippocampal injection of the MEK inhibitor U0126 prior to each phase prevents the activation of both ERK1/2 and CREB after unpaired conditioning. Block of any activation phase leads to memory impairment. We finally reveal that the biphasic activation of ERK/CREB activity is independently regulated, yet both phases are critically required for the consolidation of long-term memories following unpaired fear conditioning. These data provide compelling evidence that CA1 serves different forms of memory by expressing differential cellular mechanisms that are dependent on the training regime.
authors.affiliation: Laboratoire de Neurosciences Cognitives, Centre National de la Recherche Scientifique, CNRS UMR 5106, Université de Bordeaux I, 33605 Talence, France.
authors.forename: Pierre
authors.initials: P
authors.lastname: Trifilieff
authors.forename: Cyril
authors.initials: C
authors.lastname: Herry
authors.forename: Peter
authors.initials: P
authors.lastname: Vanhoutte
authors.forename: Jocelyne
authors.initials: J
authors.lastname: Caboche
authors.forename: Aline
authors.initials: A
authors.lastname: Desmedt
authors.forename: Gernot
authors.initials: G
authors.lastname: Riedel
authors.forename: Nicole
authors.initials: N
authors.lastname: Mons
authors.forename: Jacques
authors.initials: J
authors.lastname: Micheau
mesh_terms: D000818:Animals; D001245:Association Learning / Q000502:physiology; D003214:Conditioning, Classical / Q000502:physiology*; D017362:Cyclic AMP Response Element-Binding Protein / Q000378:metabolism*; D004777:Environment; D019706:Excitatory Postsynaptic Potentials / Q000502:physiology; D048049:Extracellular Signal-Regulated MAP Kinases / Q000378:metabolism*; D005239:Fear / Q000502:physiology*; D006624:Hippocampus / Q000378:metabolism*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D015398:Signal Transduction / Q000502:physiology; D018709:Statistics, Nonparametric; D013997:Time Factors
chemical_list: D017362:Cyclic AMP Response Element-Binding Protein; D048049:Extracellular Signal-Regulated MAP Kinases