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The Journal of Neuroscience, January 15, 2002, 22(2):577-583
Prefrontal Cortex Long-Term Potentiation, But Not Long-Term
Depression, Is Associated with the Maintenance of Extinction of Learned
Fear in Mice
Cyril
Herry1 and
René
Garcia2
1 Laboratoire de Neurosciences Cognitives, Centre
National de la Recherche Scientifique Unité Mixte de Recherche
5106, Université de Bordeaux I, 33405 Talence, France, and
2 Laboratoire de Psychophysiologie, Faculté des
Sciences, Université de Nice-Sophia Antipolis, 06108 Nice, France
Considerable efforts have been made to identify changes of brain
synaptic plasticity associated with fear conditioning. However, for
both clinical applications and our fundamental understanding of memory
processes, it appears also necessary to investigate synaptic plasticity
related to extinction. We previously showed that extinction of freezing
to a tone conditioned stimulus (CS; previously paired with footshock)
in mice results in a sequence of depression and potentiation of
synaptic efficacy in the medial prefrontal cortex (mPFC). These data as
well as those from lesion studies suggest that the direction of changes
in prefrontal synaptic plasticity may modulate extinction of learned
fear. To test this, we analyzed the effects of low-frequency
stimulation (LFS) and high-frequency stimulation (HFS) of the
mediodorsal thalamic nucleus, known to induce prefrontal
long-term depression (LTD) and potentiation (LTP), respectively, on
extinction. We found that maintenance of the depression phase, using
thalamic LFS, was associated with resistance to extinction. Thalamic
HFS applied before extinction testing had no effect on the rate of
extinction. However, 1 week follow-up tests revealed that the memory of
extinction was intact in these mice (with prefrontal LTP) and in
control mice displaying prefrontal LTP-like changes, whereas control
mice that did not exhibit such changes displayed a return of freezing
to the CS. The results suggest that after extinction the lack of
depression-LTP-like conversion sequence in the mPFC synaptic efficacy
may profoundly alter the process of consolidation.
Key words:
fear conditioning; extinction; long-term depression; long-term potentiation; medial prefrontal cortex; mouse
Copyright © 2002 Society for Neuroscience 0270-6474/02/222577-07$05.00/0
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