Foreground contextual fear memory consolidation requires two independent phases of hippocampal ERK/CREB activation

P Trifilieff, C Herry, P Vanhoutte, J Caboche… - Learning & …, 2006 - learnmem.cshlp.org
P Trifilieff, C Herry, P Vanhoutte, J Caboche, A Desmedt, G Riedel, N Mons, J Micheau
Learning & memory, 2006learnmem.cshlp.org
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 …
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.
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