Amygdala modulation of memory-related processes in the hippocampus: potential relevance to PTSD.

A key assumption in the study of stress-induced cognitive and neurobiological modifications is that alterations in hippocampal functioning after stress are due to an excessive activity exerted by the amygdala on the hippocampus. Research so far focused on stress-induced impairment of hippocampal plasticity and memory but an exposure to stress may simultaneously also result in strong emotional memories. In fact, under normal conditions emotionally charged events are better remembered compared with neutral ones. Results indicate that under these conditions there is an increase in activity within the amygdala that may lead to memory of a different quality. Studying the way emotionality activates the amygdala and the functional impact of this activation we found that the amygdala modulates memory-related processes in other brain areas, such as the hippocampus. However, this modulation is complex, involving both enhancing and suppressing effects, depending on the way the amygdala is activated and the hippocampal subregion examined. The current review summarizes our findings and attempts to put them in context with the impact of an exposure to a traumatic experience, in which there is a mixture of a strong memory of some aspects of the experience but impaired memory of other aspects of that experience. Toward that end, we have recently developed an animal model for the induction of predisposition to stress-related disorders, focusing on the consequences of exposure to stressors during juvenility on the ability to cope with stress in adulthood. Exposing juvenile-stressed rats to an additional stressful challenge in adulthood revealed their impairment to cope with stress and resulted in significant elevation of the amygdala. Interestingly, and similar to our electrophysiological findings, differential effects were observed between the impact of the emotional challenge on CA1 and dentate gyrus subregions of the hippocampus. Taken together, the results indicate that long-term alterations within the amygdala contribute to stress-related mnemonic symptoms and suggest that elucidating further these intra-amygdala alterations and their effects on modulating other brain regions is likely to be beneficial for the development of novel approaches to treat stress-related disorders.

Differential activation of hippocampus and amygdala following spatial learning under stress.

We examined the activation of memory-related processes in the hippocampus and the amygdala following spatial learning under stress, in the rat. Animals were trained in a water maze in a massed spatial task under two stress conditions (cold and warm water). In the dorsal CA1, training was accompanied by increased phosphorylation of ERK2 only in animals that have acquired the task (irrespective of whether they were trained in cold or warm water). In the amygdala, significant activation of ERK2 was found only in animals that learned the task well under high levels of stress. Hence, the results suggest that the amygdala and the hippocampus are differentially activated following spatial learning, depending on the level of stress involved.

Short-term behavioral and electrophysiological consequences of underwater trauma.

In a previous work we found that a 30-s underwater trauma, following 8 days of training for a spatial memory task in the water maze, resulted in poor performance in the spatial memory task at both 1 h and 3 weeks after the trauma. Here we found that compared with naive animals and animals that were trained for the spatial learning task but were not traumatized, the traumatized rats showed impaired performance in a spatial learning task in the water maze 20 min after the trauma and a reduced level of dentate gyrus long-term potentiation (LTP) 40 min after high-frequency stimulation to the perforant path. We also found a positive correlation between the behavioral performance and hippocampal plasticity. The reduced ability to induce LTP suggests that the trauma-related behavioral impairment is mediated by hippocampal-dependent processes. The underwater trauma may provide an important and potentially powerful model for understanding the mechanisms underlying the relationship between stress, cognition, and learning.

Amygdala-hippocampus dynamic interaction in relation to memory.

Typically the term "memory" refers to the ability to consciously remember past experiences or previously learned information. This kind of memory is considered to be dependent upon the hippocampal system. However, our emotional state seems to considerably affect the way in which we retain information and the accuracy with which the retention occurs. The amygdala is the most notably involved brain structure in emotional responses and the formation of emotional memories. In this review we describe a system, composed of the amygdala and the hippocampus, that acts synergistically to form long-term memories of significantly emotional events. These brain structures are activated following an emotional event and cross-talk with each other in the process of consolidation. This dual activation of the amygdala and the hippocampus and the dynamics between them may be what gives emotionally based memories their uniqueness.

Biphasic modulation of hippocampal plasticity by behavioral stress and basolateral amygdala stimulation in the rat.

Explicit memory may depend on the hippocampus, whereas the amygdala may be part of an emotional memory system. Priming stimulation of the basolateral group of the amygdala (BLA) resulted in an enhanced long-term potentiation (LTP) in the dentate gyrus (DG) to perforant path (PP) stimulation 30, 90, 150, and 180 min after high-frequency stimulation (HFS). Exposure of rats to a behavioral stress is reported to inhibit DG LTP. Because the amygdala is thought to mediate emotional responses, we examined the apparent discrepancy between the effects of behavioral stress induced 1 hr before HFS to the PP and of amygdala priming on hippocampal plasticity by stimulating the BLA 1 hr before HFS to the PP. The two delayed protocols inhibited the expression of LTP to PP stimulation, whereas priming the BLA immediately before HFS to the PP enhanced DG LTP. Moreover, exposure to the behavioral stress blocked the enhancing effects of BLA priming on LTP. We propose that the activation of the BLA (either by behavioral stress or by direct electrical stimulation) has a biphasic effect on hippocampal plasticity: an immediate excitatory effect and a longer-lasting inhibitory effect.

Priming stimulation in the basolateral amygdala modulates synaptic plasticity in the rat dentate gyrus.

We investigated the effects of basolateral amygdala (BLA) priming on long-term potentiation (LTP) in the dentate gyrus (DG). In the control animals, the induction of high-frequency stimulation (HFS) to the perforant path (PP) resulted in hippocampal LTP at all the time intervals tested. A priming stimulation to the BLA prior to the application of HFS to the PP resulted in the enhancement of the excitatory post-synaptic potential (EPSP)-LTP and population spike (PS)-LTP in the DG from 90-min post-HFS onwards. These findings suggest that the amygdala has a potential role in the modulation of some aspects of memory that are mediated by the hippocampus.