Browsing by Author "Kwapis, Janine L."

Now showing 1 - 3 of 3
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    Activity Dependent Protein Degradation Is Critical for the Formation and Stability of Fear Memory in the Amygdala
    Jarome, Timothy J.; Werner, Craig T.; Kwapis, Janine L.; Helmstetter, Fred J. (PLOS, 2011-09)
    Protein degradation through the ubiquitin-proteasome system [UPS] plays a critical role in some forms of synaptic plasticity. However, its role in memory formation in the amygdala, a site critical for the formation of fear memories, currently remains unknown. Here we provide the first evidence that protein degradation through the UPS is critically engaged at amygdala synapses during memory formation and retrieval. Fear conditioning results in NMDA-dependent increases in degradationspecific polyubiquitination in the amygdala, targeting proteins involved in translational control and synaptic structure and blocking the degradation of these proteins significantly impairs long-term memory. Furthermore, retrieval of fear memory results in a second wave of NMDA-dependent polyubiquitination that targets proteins involved in translational silencing and synaptic structure and is critical for memory updating following recall. These results indicate that UPS-mediated protein degradation is a major regulator of synaptic plasticity necessary for the formation and stability of long-term memories at amygdala synapses.
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    GluR2 endocytosis-dependent protein degradation in the amygdala mediates memory updating
    Ferrara, Nicole C.; Jarome, Timothy J.; Cullen, Patrick K.; Orsi, Sabrina A.; Kwapis, Janine L.; Trask, Sydney; Pullins, Shane E.; Helmstetter, Fred J. (Springer Nature, 2019-03-26)
    Associations learned during Pavlovian fear conditioning are rapidly acquired and long lasting, providing an ideal model for studying long-term memory formation, storage, and retrieval. During retrieval, these memories can "destabilize" and become labile, allowing a transient "reconsolidation" window during which the memory can be updated, suggesting that reconsolidation could be an attractive target for the modification of memories related to past traumatic experiences. This memory destabilization process is regulated by protein degradation and GluR2-endocytosis in the amygdala. However, it is currently unknown if retrieval-dependent GluR2-endocytosis in the amygdala is critical for incorporation of new information into the memory trace. We examined whether the addition of new information during memory retrieval required GluR2-endocytosis to modify the original memory. The presentation of two foot shocks of weaker intensity during retrieval resulted in GluR2 endocytosis-dependent increase in fear responding on a later test, suggesting modification of the original memory. This increase in fear expression was associated with increased protein degradation and zif268 expression in the same population of cells in the amygdala, indicating increased destabilization processes and cellular activity, and both were lost following blockade of GluR2-endocytosis. These data suggest that the endocytosis of GluR2-containing AMPA receptors in the amygdala regulates retrieval-induced strengthening of memories for traumatic events by modulating cellular destabilization and activity.
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    Special Issue “Molecular Mechanisms of Memory Formation and Modification”
    Jarome, Timothy J.; Kwapis, Janine L. (MDPI, 2021-04-16)
    Memory is vital to human functioning and controls future behavioral responses [...]