The role of the noradrenergic system in emotional memory
Introduction
Almost 15 years ago, The Netherlands were shocked by an event that was unique to our history: the “Bijlmer Disaster”. In this airplane disaster, on October 4th, 1992 a Boeing 747 air freighter crashed on two apartment buildings in the southeastern part of Amsterdam, and took the lives of 43 people. This event had an enormous emotional impact and triggered all aspects that have been studied and analyzed in the psychological and medical literature about the traumatic memory processes (Brewin, 2003, McNally, 2003). Testimonies on the event varied enormously in content and were highly debated. It is illustrative for the complexity of traumatic memories and emotional information processing. It highlights the fact that a disaster can cause a wide range of emotions that are accompanied by both physical arousal and a noticeable impact on memory.
From an evolutionary point of view it seems logical that a confrontation with a stressful situation is better remembered than a neutral situation, resulting in a more adequate reaction in a similar situation. This reasoning led to a widely accepted view that the memory for emotional information is generally better than for neutral information (Cahill and McGaugh, 1998, McGaugh, 2000).
The research reviewed here, focuses specifically on the neurobiological basis of stress, emotion, arousal and their effect on memory. This contribution, studies in particular the role of noradrenaline as neurotransmitter and stress hormone in emotional memory1 processing.
Section snippets
Sources of adrenaline and noradrenaline (NA)
Adrenaline and noradrenaline, also known as epinephrine (EPI) and norepinephrine (NE), are two separate but related hormones secreted by the medulla of the adrenal glands. These compounds are also produced at the ends of sympathetic nerve fibres, where they serve as chemical mediators for conveying the nerve impulses to the effector organs. Noradrenaline is formed in the body from the amino acid tyrosine, and adrenaline is in turn formed from noradrenaline (Kalat, 1992). Chemically the two
Animal studies on noradrenergic modulation of memory in stress tasks
A wide array of animal studies has focused on the effect of stress hormones on memory performance in rats. In these studies a great variety of hormones and neurotransmitters have been tested that were either systemically injected or injected in relevant brain areas, such as the amygdalar complex (LeDoux, 2000, McGaugh and Introini-Collison, 1987, McGaugh et al., 1993). Adrenaline and its agonists applied at encoding or immediately post-training increase memory performance in all types of stress
Human studies on noradrenergic modulation of emotional memory
The effects of NA manipulations on long-term emotional memory has been explored in several (although a limited number of) human studies. Propranolol, a β1–β2 noradrenergic receptor blocker that easily crosses the blood brain barrier was predominantly used to explore the effect of NA on memory. One of the first human studies that changed the focus from a cognitive perspective to a more neurobiological viewpoint was of Cahill, Prins, Weber, and McGaugh (1994). They adjusted a slide show, used as
Animal studies
The role of β-adrenergic receptors during reconsolidation has been tested in a few animal studies, based on the hypothesis that a time-dependent consolidation process occurs each time a memory is reactivated (Przybyslawski, Roullet, & Sara, 1999). The role of beta noradrenergic receptors in reconsolidation in rats was examined in both a positively reinforced radial maze task and a footshock-reinforced conditioned emotional response task. In the maze task, rats were trained over several days in
Interaction between NA and cortisol and effects on memory
Although this contribution is mainly directed at the role of NA in emotional memory it is evident that other stress hormones are playing a role in the final effect on memory. The role of cortisol has been investigated extensively in animals and humans. The role of glucocorticoids and cortisol and the interaction with noradrenaline will be extensively summarized elsewhere (see Wolf, 2008).
With respect to cortisol, facilitating effects as well as impairing effects on cognitive performance have
Role of the amygdala
It became clear from several studies on patients with brain damage that the amygdalae are essential nuclei in the brain in the labeling, perception, encoding and other aspects of emotional memory (Adolphs et al., 1997, Anderson and Phelps, 2001). In an early study on two patients with Urbach-Wiethe disease, the consequences of primary amygdala damage on memory performance became evident. Both patients had circumscribed, bilaterally symmetrical damage confined to the amygdaloidal region, while
Noradrenergic modulation of the human amygdala
Intrigued by findings from imaging studies about the involvement of the amygdala in emotional memory processing from perception to retrieval (see above (Phan et al., 2002, Zald, 2003)), we designed and carried out an fMRI study on healthy human subjects (van Stegeren et al., 2005).
The design of this fMRI study was based on our previous findings that 1) β-adrenergic blockade by propranolol was effective in blocking the enhancement in memory for emotional material under placebo condition in
Noradrenergic effects in other brain areas
Most studies on the site of action of NA in emotional memory have been directed at the amygdala. But there are also other brain areas involved in the circuitry that determines noradrenaline effects on memory performance.
Two areas worth mentioning are the hippocampus and the prefrontal cortex (PFC), connected with ascending noradrenergic projections from the locus coeruleus and reciprocally connected with the amygdala. The hippocampus is involved in the formation of new memories. It is also
Gender effects
Exploring possible gender and/or lateralization effects in emotional information processing and memory, we reached three conclusions. First, the amygdala activation patterns during encoding are highly similar in men and women, with a left lateralization for emotionally laden pictures in all subjects (van Stegeren et al., 2005). This preference for a predominantly left hemispheric (here a left amygdalar) activation during confrontation with (negative) emotional stimuli is a relatively robust
Therapeutic application of betablockers in PTSD
From a theoretical point of view, applying betablockers in the (secondary) prevention of PTSD seems to be a logical possibility that could be part of the therapeutic palette. However, some discussion on this topic has arisen (Giles, 2005, Larkin, 1999, van Stegeren, 2005, Vince, 2005).
An objection that could be raised against the preventive use of betablockers is that it has not been indisputably established experimentally that betablockade is effective during the consolidation phase i.c. after
Ethical considerations
Ethical concerns, such as fears that prescribing betablockers might impair a persons ability to judge what is morally acceptable, have been raised, for example, by a member of the US President’s Council on Bioethics (Giles, 2005). The concern is, that betablockers could alter the conscience of a person and that these drugs take out the ‘feeling’ or ‘emotionality’ of people, hence creating human robots without ethical considerations.
There is rather a strong evidence to refute these fears. In all
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