PKM zeta Inhibition Disrupts Reconsolidation and Erases Object Recognition Memory

摘要

Object recognition memory (ORM) confers the ability to discriminate the familiarity of previously encountered items. Reconsolidation is the process by which reactivated memories become labile and susceptible to modifications. The hippocampus is specifically engaged in reconsolidation to integrate new information into the original ORM through a mechanism involving activation of brain-derived neurotrophic factor (BDNF) signaling and induction of LTP. It is known that BDNF can control LTP maintenance through protein kinase M zeta (PKM zeta), an atypical protein kinase C isoform that is thought to sustain memory storage by modulating glutamatergic neurotransmission. However, the potential involvement of PKM zeta in ORM reconsolidation has never been studied. Using a novel ORM task combined with pharmacological, biochemical, and electrophysiological tools, we found that hippocampal PKM zeta is essential to update ORM through reconsolidation, but not to maintain the inactive recognition memory trace stored over time, in adult male Wistar rats. Our results also indicate that hippocampal PKM zeta acts downstream of BDNF and controls AMPAR synaptic insertion to elicit reconsolidation and suggest that blocking PKM zeta activity during this process deletes active ORM.