Foreground contextual fear memory consolidation requires two independent phases of hippocampal ERK/CREB activation.
1. Learn Mem. 2006 May-Jun;13(3):349-58. Epub 2006 May 16.
Foreground contextual fear memory consolidation requires two independent phases
of hippocampal ERK/CREB activation.
Trifilieff P(1), Herry C, Vanhoutte P, Caboche J, Desmedt A, Riedel G, Mons N,
(1)Laboratoire de Neurosciences Cognitives, Centre National de la Recherche
Scientifique, CNRS UMR 5106, Université de Bordeaux I, 33605 Talence, France.
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
PMID: 16705140 [Indexed for MEDLINE]