A possible role for PKM ! / ZIP target in the maintenance of hippocampal inhibitory gating to protect from excessive fear after memory retrieval

Impaired modulation of emotional memory is a feature of several affective disorders, including depression, anxiety and PTSD. AMPA receptor trafficking during the first hours after memory retrieval is crucial in modulation of emotional memory. We unknown targets, when applied via cannulas into the dorsal hippocampus 6 h after memory retrieval, was able to normalize the GluA2 up regulation and the increase in retrieval-induced decay. There were no retrograde effects of ZIP on memory expression when ZIP was given 24 h after retrieval. Moreover, no unspecific effects of the ZIP peptide or its scrambled control were observed. Unlike its disputed role in memory maintenance in the amygdala, PKM!, or the yet unknown targets of ZIP, exerts a well-timed inhibitory constraint on memory strengthening in the lingering process of reconsolidation, by maintaining GluA2-containing glutamate receptors at hippocampal synapses. In this way it might act to protect from excessive fear after memory retrieval. Thus, ZIP targets are interesting for the mechanistic dissection and potential treatment of aberrant fear. Role of PKM!/ZIP target after retrieval of fear memory