Remembering Stressful Events: Situations surrounding emotional events are better remembered than others that accompany neutral events. However, in severe pathological states such as posttraumatic stress disorder (PTSD), exposure to threatening situations can also result in memory impairment. In this case, a hypermnesia for a salient trauma-related cue is associated with loss of memory for important aspects of the traumatic event. The memory for the core traumatic event is enhanced, but the capacity to place it in the right place and in response to the right cues is reduced. Kaouane et al. (p. 1510 , published online 23 February) associated a high-intensity threat with the infusion of corticosterone in the hippocampus to induce PTSD-like memory impairments in mice. The animals became unable to identify the threat context as the right predictor of the threat, and they showed a fear response for discrete salient cues normally identified as safe. The neural activation patterns in the amygdala and hippocampal regions of these mice were similar to those observed in human PTSD.

Vitamin A and its derivatives, the retinoids, have been implicated recently in the synaptic plasticity of the hippocampus and might therefore play a role in associated cognitive functions. Acting via transcription factors, retinoids can regulate gene expression via their nuclear receptors [retinoic acid receptors (RARs) and retinoid X receptors]. In a series of experiments, the present study investigated the possible role of age-related downregulation of retinoid-mediated transcription events in the cognitive decline seen in aged mice. We observed that the brain (and hippocampal) levels of retinoid receptors and the expression of specific associated target genes were restored to presenescent (adult) levels in aged mice after acute administration (150 μg/kg, s.c.) of retinoic acid (RA). These effects of RA, however, could be abolished by the coadministration of an RAR antagonist. RA was also demonstrated to alleviate the age-related deficit in the CA1 long-term potentiation efficacy of aged micein vivo. Moreover, RA was found to alleviate completely the performance deficit of aged mice to the control level in a two-stage spatial discrimination paradigm designed to assess relational memory. This promnesic effect of RA was again susceptible to abolition by RAR antagonist treatment. The parallel molecular, cellular, and behavioral correlates associated with the decrease of retinoid receptor expression and its normalization demonstrated here suggest that the fine regulation of retinoid-mediated gene expression is fundamentally important to optimal brain functioning and higher cognition. Specifically, a naturally occurring dysregulation of retinoid-mediated molecular events might be a potential etiological factor for cognitive deterioration during senescence.