Glutamate receptor mediated bi-directional plasticity is responsible for reconsolidation of fear memories
Type of DegreeDissertation
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Retrieval of a memory appears to render it unstable until the memory is once again re-stabilized or reconsolidated. Although the occurrence and consequences of reconsolidation have received much attention in recent years, the specific mechanisms that underlie the process of reconsolidation have not been fully described. Here, we present the first electrophysiological model of the synaptic plasticity changes underlying the different stages of reconsolidation of a conditioned fear memory. In this model, retrieval of a fear memory results in immediate but transient alterations in synaptic plasticity, mediated by modified expression of the glutamate receptor subunits GluA1, GluA2, and GluN2B. Retrieval of a memory results in an immediate impairment in Long Term Potentiation (LTP), which recovers 6 h following memory retrieval. Conversely, memory retrieval results in an immediate enhancement of Long Term Deppression (LTD), which decreases with time. These changes in plasticity are accompanied by increased immediate expression of GluN2B and decreased expression of GluA1/2 receptor subunits. Recovery of LTP and LTD correlates with progressive normalization in GluN2B expression (return to pre-retrieval levels), and subsequent overexpression of GluA2 receptor subunits (above pre-retrieval levels). The contribution of each receptor was confirmed by interfering with receptor expression at the postsynaptic sites. Blocking GluA2 endocytosis restored LTP and attenuated LTD during the initial portion of the reconsolidation period, while antagonism of GluN2B attenuated LTD. These findings suggest that altered glutamate receptor expression controls different forms of synaptic plasticity during reconsolidation.