[HTML][HTML] Disruption of AMPA receptor endocytosis impairs the extinction, but not acquisition of learned fear

GL Dalton, YT Wang, SB Floresco… - …, 2008 - nature.com
Neuropsychopharmacology, 2008nature.com
Synaptic plasticity in the form of long-term potentiation (LTP) plays a critical role in the
formation of a Pavlovian fear association. However, the role that synaptic plasticity plays in
the suppression of a learned fear response remains to be clarified. Here, we assessed the
role that long-term depression (LTD) plays in the acquisition, expression, and extinction of a
conditioned fear response. We report that blockade of LTD with a GluR2-derived peptide
(Tat-GluR2 3Y; 1.5 μmol/kg, iv) that blocks regulated α-amino-3-hydroxy-5-methyl-isoxazole …
Abstract
Synaptic plasticity in the form of long-term potentiation (LTP) plays a critical role in the formation of a Pavlovian fear association. However, the role that synaptic plasticity plays in the suppression of a learned fear response remains to be clarified. Here, we assessed the role that long-term depression (LTD) plays in the acquisition, expression, and extinction of a conditioned fear response. We report that blockade of LTD with a GluR2-derived peptide (Tat-GluR2 3Y; 1.5 μmol/kg, iv) that blocks regulated α-amino-3-hydroxy-5-methyl-isoxazole-4-propionic acid (AMPA) receptor endocytosis during an initial extinction training session disrupted both the expression and recall of extinction learning. A similar impairment of extinction during training, but not recall, was observed when NMDA receptor-dependent LTD was inhibited through the selective blockade of NMDA NR2B receptors with Ro 25-6981. In contrast, blockade of LTD with Tat-GluR2 3Y during fear conditioning or during a fear recall test did not effect the expression or recall of either contextual or cue-induced conditioned fear. Similarly, administration of Tat-GluR2 3Y prior to an extinction recall test did not affect spontaneous recovery or rate of re-extinction in previously extinguished rats. These data demonstrate that AMPA receptor endocytosis does not mediate acquisition or expression of conditioned fear, but may play a role in the extinction of fear memories. Furthermore, these findings suggest that LTD may be a molecular mechanism that facilitates the selective modification of a learned association while leaving intact the ability to form a new memory.
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