Specific cells and synapses within implicated neural circuits are recruited during learning, such that memory allocation is not random but rather is regulated by precise mechanisms which define where and how information is stored within the neural network [1]. Nearly four decades ago, Seymour Kety suggested that emotionally arousing experiences may be associated with activation of the locus coeruleus, sending adrenergic projections to different regions of the brain (such as hippocampus, cortex and cerebellum) [2]. Moreover, he proposed that activation of β-adrenoreceptors by released norepinephrine (NE) could result in facilitation of synaptic transmission through the mechanism involving increases in the intracellular cAMP concentration and new protein synthesis, thus contributing to the memory acquisition and maintenance. It is currently hypothesized that synaptic plasticity, specifically long-term potentiation (LTP), in the neural circuits of learned behaviors could provide a cellular substrate of memory storage [3]. Consistent with Kety's proposal, it has been demonstrated recently that direct activation of the locus coeruleus initiated protein synthesis-dependent LTP at the perforant path input to the dentate gyrus in awake rats [4]. At the behavioral level, there is overwhelming evidence that emotionally-charged events often lead to the creation of vivid long-lasting memories [5, 6], in part due to a surge of norepinephrine and subsequent stimulation of adrenergic receptors in the nervous system [7, 8], and, as a result, improved memory consolidation [6]. Unexpectedly, recent studies of the human subjects indicate that although emotionally-charged events are remembered better than emotionally neutral experiences, emotion may enhance the subjective sense of recollection more than memory accuracy [9].

The results of numerous previous experiments implicate the amygdala in acquisition and retention of memory for emotionally charged events [reviewed in [10–12]]. Thus synaptic enhancements in the conditioned stimulus (CS) pathways to the lateral nucleus of the amygdala were shown to contribute in the acquisition of fear memory to the acoustic CS during auditory fear conditioning [13–17]. It has been demonstrated also that the basolateral amygdala can regulate consolidation of memories in other regions of the brain [6, 18]. The contribution of the amygdala to modulating memory consolidation critically depends on activation of β-adrenoreceptors in the BLA [19–21]. According to the emotional tagging concept, activation of the amygdala during emotionally arousing events could mark the experience as important and aid in enhancing synaptic plasticity in other regions of the brain [22]. Consistent with this notion, it has been shown previously that the actions of NE in the BLA promote the induction of LTP [23] and the expression of Arc protein, implicated in mechanisms of synaptic plasticity and memory formation, in the hippocampus [24]. On the other hand, plasticity in the auditory thalamus (specifically in the medial division of the medial geniculate nucleus and posterior intralaminar nucleus), prior to projections to the LA, plays an essential role in auditory fear conditioning [25, 26]. This supports the notion that plasticity in multiple regions of the brain may contribute to the formation of fear memory [26].

Recent reviews have examined the role of the noradrenergic system in emotional memory [27], the influence of norepinephrine on fear circuitry [28], and the function of norepinephrine system in general [29]. Learning to recognize important cues in our environment with emotional salience, such as danger or altruistic social interactions, is an essential survival mechanism. Thus evolution has shaped our nervous system to robustly remember cues that elicit emotion. While some emotional responses are hard-wired into the brain's circuitry, many of them are learned through experience [10]. How do we remember emotionally charged events so well, and what does it tell us about the mechanisms of memory storage in the brain? Most of our experiences and information detected by our senses are not remembered. How does our brain know what events are important enough to be preserved for long-term storage? One important clue comes from the fact that the transition of the behavioral experiences into memory likely arises from changes in the efficiency of synaptic transmission in corresponding neuronal pathways [30–32, 15]. In this review we will consider at the level of changes in synaptic function how creation of long-lasting memories during emotional arousal might be linked to a surge of norepinephrine in specific neural circuits.