Hippocampal structural plasticity accompanies the resulting contextual fear memory following stress and fear conditioning

Abstract

The present research investigated the resulting contextual fear memory and structural plasticity changes in the dorsal hippocampus (DH) following stress and fear conditioning. This combination enhanced fear retention and increased the number of total and mature dendritic spines in DH. Intra-basolateral amygdala (BLA) infusion of midazolam prior to stress prevented both the enhancement of fear retention and an increase in the density of total and mature dendritic spines in DH. These findings emphasize the role of the stress-induced attenuation of GABAergic neurotransmission in BLA in the promoting influence of stress on fear memory and on synaptic remodeling in DH. In conclusion, the structural remodeling in DH accompanied the facilitated fear memory following a combination of fear conditioning and stressful stimulation.It is well accepted that prior exposure to stressful events facilitates the emergence of fear memory (Shors et al. 1992;Beylin and Shors 1998;Shors 2001;Cordero et al. 2003;Rodriguez Manzanares et al. 2005). Consistent with this, recent data shows that the interaction of an unrelated aversive experience and an established fear memory trace results in a robust and persistent fear memory (Giachero et al. 2013). This stress-induced promoting influence was prevented by midazolam (MDZ) intra-basolateral amygdala (BLA) infusion prior to stress, indicating that such an influence is related to the modulation of the GABAergic transmission in BLA (Giachero et al. 2013).Dendritic spines represent the structural platform for excitatory synaptic contacts between neurons (Gray 1959;Chapleau and Pozzo-Miller 2007), with growing evidence suggesting that synaptic remodeling accompanies the formation of long-term memory (Restivo et al. 2009). In line with this view, the encoding of a novel contextual representation was shown to result in a rapid synaptic rearrangement through an increase in spine density, particularly in the hippocampus across multiple memory paradigms, including contextual fear memory (Leuner et al. 2003;Restivo et al. 2009;Vetere et al. 2011).The dorsal hippocampus (DH) is crucially involved in the contextual representation following fear conditioning (Kim and Fanselow 1992;Phillips and LeDoux 1995;Maren and Fanselow 1997;Fanselow and Dong 2010). Related to this, the present research investigates the structural plasticity in the DH that may underlie the contextual fear memory resulting from the interaction of fear conditioning and an unrelated stressful experience. The BLA is an essential component of the neural circuitry orchestrating emotional response to threatening stimuli (LeDoux 2000), and compelling evidence has shown that the activation of GABAa sites, specifically in BLA prior to stress, attenuates the enhancement of fear memory (Rodriguez Manzanares et al. 2005;Giachero et al. 2013). Therefore, we also explored the modulatory role of the GABAergic neurotransmission in the BLA in both fear retention and structural plasticity in the DH, which is potentially associated with the fear memory...

Social factors modulate restraint stress induced hyperthermia in mice

“…There have been much experimental researches demonstrating stress-induced memory enhancing effects (Giachero et al, 2013;Luine et al,1996;Mays et al, 2010;Yuen et al, 2011), but detailed mechanisms of this effect are not well clarified. The consistency among three stress-induced responses (SIH, memory enhancing and elevated of corticosterone levels) suggests integration of the stress-induced responses through different pathways, because autonomic response is mediated by the HPA axis and stress-induced behavioral responses are mediated by corticotropin-releasing hormone (Müller et al, 2003).…”

Fear Memory

“…Stress enhances fear learning, a process mediated by the basolateral amygdala (BLA) (FIGURE 1A), which has been shown recently to modulate hippocampal plasticity and dendritic growth (201,202,389). Repeated stress enhances learned fear through a brain action mediated by ␤-adrenoceptors and raises impulsivity through a separate mechanism (109).…”

“…Emotional arousal with BLA activation is generally viewed as essential for good memory consolidation of fear tasks (401,403,404) and is at the root of the well-known facilitation of fear learning by stress (201,202) as mentioned above in section IA. Blockade of the memory consolidation of IA is obtained with pre-or posttraining infusions of the classic N-methyl-D-aspartate (NMDA) receptor antagonist D-amino-5-phosphonic acid (AP5) into either CA1 (267) or BLA (343).…”

Hippocampal dendritic spines remodeling and fear memory are modulated by GABAergic signaling within the basolateral amygdala complex

“…It is well established that dendritic spines express the structural platform for excitatory synaptic contacts between neurons (Yuste and Denk, ). Besides, hippocampal structural plasticity, in the form of changes in spine density following learning, provides a substrate for the storage of long‐term memories, including contextual fear memories (Kandel, ; Restivo et al, ; Giachero et al, ) although to date, no studies report whether stress‐induced changes on the GABAergic transmission in BLA affect the structural rearrangement in DH associated with fear memory.…”