The Journal of Neuroscience, February 1, 2003, 23(3):737
BRIEF COMMUNICATION
Inhibition of mRNA and Protein Synthesis in the CA1 Region of the
Dorsal Hippocampus Blocks Reinstallment of an Extinguished Conditioned
Fear Response
Martín
Cammarota1, 2,
Lia R. M.
Bevilaqua1,
Daniel
Kerr1,
Jorge H.
Medina2, and
Iván
Izquierdo1
1 Memorial Center, Department of Biochemistry,
Instituto de Ciências Biológicas e da Saúde, Federal
University of Río Grande do Sul, Porto Alegre 90035-003, RS, Brazil, and 2 Neuroreceptor Laboratory,
Institute of Cellular Biology and Neurosciences, Faculty of Medicine,
University of Buenos Aires, Buenos Aires 1121, Argentina
Memories are extinguished by the repeated presentation of a
conditioned stimulus in the absence of an unconditioned stimulus to
which it has been associated. It is believed that extinction establishes a new hierarchy of responses rather than an actual forgetting of the original response, which can usually reappear spontaneously after interruption of the extinction process. In this
study, our aim was to analyze how profound extinction can be. Rats were
trained in a one-trial, step-down inhibitory avoidance paradigm and
then were exposed to several extinction sessions in which they were
allowed to freely explore the apparatus for 30 sec after having stepped
down. Extinction was complete enough so that there was no spontaneous
recovery, and test session performance could not be enhanced by
pharmacological agents with well known facilitative actions on
retrieval. After being submitted to a new training session, control
animals reacquired the avoidance response; however, animals failed to
do so after receiving bilateral intra-CA1 infusions of either the
protein synthesis inhibitor anisomycin or the mRNA synthesis blocker
5,6-dichloro-1-
-d-ribofuranosyl benzimidazole 15 min before the
retraining session. Our results indicate that extinction can be carried
to a point at which reinstallment of the conditioned response requires,
like the original learning, de novo gene expression and
protein synthesis in the CA1 region of the dorsal hippocampus.
Key words:
memory; learning; extinction; reinstallment,
hippocampus; protein synthesis; gene expression
Copyright © 2003 Society for Neuroscience 0270-6474/03/233737-05$05.00/0
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