Activation of a remote (1-year old) emotional memory interferes with the retrieval of a newly formed hippocampus-dependent memory in rats

Abstract

The persistent intrusion of remote traumatic memories in people with post-traumatic stress disorder (PTSD) may contribute to the impairment of their ongoing hippocampal and prefrontal cortical functioning. In the current work, we have developed a rodent analogue of the intrusive memory phenomenon. We studied the influence of the activation of a remote traumatic memory in rats on their ability to retrieve a newly formed hippocampus-dependent memory. Adult male Sprague-Dawley rats were given inhibitory avoidance (IA) training, and then 24 h or 1, 6 or 12 months later, the same rats were trained to learn, and then remember across a 30-min delay period, the location of a hidden escape platform in the radial-arm water maze (RAWM). When IA-trained rats spent the 30-min delay period in the IA apparatus, they exhibited intact remote (1-year old) memory of the shock experience. More importantly, activation of the rats' memory of the shock experience profoundly impaired their ability to retrieve the newly formed spatial memory of the hidden platform location in the RAWM. Our finding that reactivation of a remote emotional memory exerted an intrusive effect on new spatial memory processing in rats provides a novel approach toward understanding how intrusive memories of traumatic experiences interfere with ongoing cognitive processing in people with PTSD.

Influence of Pre-Training Predator Stress on the Expression of c-fos mRNA in the Hippocampus, Amygdala, and Striatum Following Long-Term Spatial Memory Retrieval

“…This difference between CA1 and other hippocampal regions is consistent with lesion and fMRI studies suggesting that CA3 and the dentate gyrus play a role in acquisition, while CA1 is important for hippocampus-dependent learning and memory retrieval (Lee and Kesner, 2004; Eldridge et al, 2005). This finding is also consistent with the extensive evidence that CA1, more than other hippocampal regions, has been found across paradigms and laboratories to exhibit a potent suppression of synaptic plasticity (LTP and primed burst potentiation) in response to stress (Kim and Diamond, 2002; Diamond et al, 2007; Tsoory et al, 2008; Joëls et al, 2009) Thus, our finding that c-fos mRNA expression in CA1 was highly sensitive to increase in response to spatial learning and to be completely suppressed in response to stress parallels behavioral findings demonstrating an impairment of hippocampus-dependent memory in response to stress (Bremner et al, 1995; Joseph, 1999; Kim and Diamond, 2002; Diamond et al, 2007; Sandi and Pinelo-Nava, 2007; Schwabe et al, 2009; Schwabe and Wolf, 2010; Zoladz et al, 2010). …”

Epigenetic modification of hippocampal Bdnf DNA in adult rats in an animal model of post-traumatic stress disorder

“…In related work, we have shown that shock avoidance conditioning in rats can exert a powerful intrusive effect on new hippocampal memory processing as much as 1 year after the original traumatic experience (Zoladz et al, 2010). Hence, the basis of such long-lasting adverse effects of emotional trauma on new memory processing in people may involve hippocampus-specific DNA methylation changes of the Bdnf gene.…”

Beneficial Effects of Tianeptine on Hippocampus-Dependent Long-Term Memory and Stress-Induced Alterations of Brain Structure and Function

“…In the experiment, rats (250–275 g; Charles River Laboratories) were injected intraperitoneally with one of five doses of tianeptine (0.25, 0.50, 1, 5, 10 mg/kg) or vehicle (0.9% saline, 1 mL/kg) and then 30 min later, the rats were given RAWM training, following previously-described methods [78,160,161,164,165,166,167,168,169,170,171]. Briefly, the rats were given 4 trials to learn the location of a hidden escape platform, which was placed at the end of one of six arms, in the RAWM.…”