Abstract
Object recognition memory (ORM) serves to distinguish familiar items from novel ones. Reconsolidation is the process by which active memories are updated. The hippocampus is engaged in ORM reconsolidation through a mechanism involving induction of long-term potentiation (LTP). The transcription factor Zif268 is essential for hippocampal LTP maintenance and has been frequently associated with memory processes. However, its possible involvement in ORM reconsolidation has not been determined conclusively. Using Zif268 antisense oligonucleotides in combination with behavioural, biochemical and electrophysiological tools in rats, we found that hippocampal Zif268 is necessary to update ORM through reconsolidation but not to retrieve it or keep it stored. Our results also suggest that knocking down hippocampal Zif268 during ORM reconsolidation deletes the active recognition memory trace.
Highlights
Object recognition memory (ORM) serves to distinguish familiar items from novel ones
When taken together with findings showing that ORM reactivation in the presence of a novel object increases Zif[268] hippocampal levels, our results indicate that this transcription factor is required to update ORM through reconsolidation and suggest that the amnesia caused by inhibition of this process with antisense oligonucleotides (ASO) is due to storage failure
ASO did not affect retention when given in dorsal CA1 6 h after ORM reactivation in the presence of a novel object (Fig. 1c) or when administered 90 min before either ORM reactivation in the presence of two familiar objects (Fig. 1d) or a 5 min-long exploration session of the training arena devoid of stimuli objects (Fig. 1e)
Summary
Object recognition memory (ORM) serves to distinguish familiar items from novel ones. Experimental evidence linking Zif[268] to declarative memory reconsolidation is scarcer In this regard, it has been reported that delayed reexposure to familiar objects causes ORM amnesia in Zif[268] knockout mice[17]. It has been reported that delayed reexposure to familiar objects causes ORM amnesia in Zif[268] knockout mice[17] These mutants were unable to exhibit late LTP or form stable hippocampus-dependent long-lasting memories[21], and had to be submitted to several learning trials to acquire an ORM trace they could remember for 48 h20. When taken together with findings showing that ORM reactivation in the presence of a novel object increases Zif[268] hippocampal levels, our results indicate that this transcription factor is required to update ORM through reconsolidation and suggest that the amnesia caused by inhibition of this process with ASO is due to storage failure. Except that sASO and ASO were administered 6 h post-RA. (d) Rats were treated as in (b), except that RA occurred in the presence of familiar objects A and B. (e) Rats were treated as in (b) except that sASO and ASO were given before a 5′-long exploration session of the training arena devoid of objects. (f) Rats were treated as in (b) except that RA was omitted. (g) Rats were treated as in (b) except that TEST was performed 3 h post-RA
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