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Post-reactivation amnesia of contextual fear memories by blockade of noradrenergic signaling has been shown to have limited replicability in rodents. This is usually attributed to several boundary conditions that gate the destabilization of memory during its retrieval. How these boundary conditions can be overcome, and what neural mechanisms underlie post-reactivation changes in contextual fear memories remain largely unknown. Here, we report a series of experiments in a contextual fear-conditioning paradigm in mice, that were aimed at solving these issues. We first attempted to obtain a training paradigm that would consistently result in contextual fear memory that could be destabilized upon reactivation, enabling post-retrieval amnesia by the administration of propranolol. Unexpectedly, our attempts were unsuccessful to this end. Specifically, over a series of experiments in which we varied different parameters of the fear acquisition procedure, at best small and inconsistent effects were observed. Additionally, we found that propranolol did not alter retrieval-induced neural activity, as measured by the number of c-Fos+ cells in the hippocampal dentate gyrus. To determine whether propranolol was perhaps ineffective in interfering with reactivated contextual fear memories, we also included anisomycin (i.e., a potent and well-known amnesic drug) in several experiments, and measures of synaptic glutamate receptor subunit GluA2 (i.e., a marker of memory destabilization). No post-retrieval amnesia by anisomycin and no altered GluA2 expression by reactivation was observed, suggesting that the memories did not undergo destabilization. The null findings are surprising, given that the training paradigms we implemented were previously shown to result in memories that could be modified upon reactivation. Together, our observations illustrate the elusive nature of reactivation-dependent changes in non-human fear memory.

A 58-year-old man was admitted to our center with an inferior ST-segment elevation myocardial infarction. A coronary angiogram showed an ectatic right coronary artery (RCA) occluded at mid vessel by a significant clot burden quantified by micro-computed tomography. Guide catheter-directed intracoronary thrombolysis with low-dose tenekteplase resulted in regaining RCA flow, when numerous efforts of manual and 'mother-child' thrombectomy had failed to achieve. A stentless strategy was followed with final thrombolysis in myocardial infarction 3 flow and angiographically insignificant stenosis remaining in the RCA. The combination of intracoronary thrombolysis and a stentless strategy is a safe and effective treatment in ST-segment elevation myocardial infarction patients with ectatic arteries and large thrombus burden when repeat manual aspiration thrombectomy fails.