Review
Interacting brain systems modulate memory consolidation

https://doi.org/10.1016/j.neubiorev.2011.11.001Get rights and content

Abstract

Emotional arousal influences the consolidation of long-term memory. This review discusses experimental approaches and relevant findings that provide the foundation for current understanding of coordinated interactions between arousal activated peripheral hormones and the brain processes that modulate memory formation. Rewarding or aversive experiences release the stress hormones epinephrine (adrenalin) and glucocorticoids from the adrenal glands into the bloodstream. The effect of these hormones on memory consolidation depends upon binding of norepinephrine to beta-adrenergic receptors in the basolateral complex of the amygdala (BLA). Much evidence indicates that the stress hormones influence release of norepinephrine in the BLA through peripheral actions on the vagus nerve which stimulates, through polysynaptic connections, cells of the locus coeruleus to release norepinephrine. The BLA influences memory storage by actions on synapses, distributed throughout the brain, that are engaged in sensory and cognitive processing at the time of amygdala activation. The implications of the activation of these stress-activated memory processes are discussed in relation to stress-related memory disorders.

Highlights

► Stress hormones contribute to fight-or-flight response and enhance memory for important events. ► The vagus nerve bridges the peripheral stress response with memory processes in the brain. ► The amygdala influences synaptic strength in other areas of the brain that are involved in memory. ► Results reveal potential underlying causes of and therapies for stress-related memory disorders.

Introduction

The usefulness of all the passions consists in their strengthening and prolonging in the soul thoughts which are good for it to conserve…

Descartes, The Passions of the Soul, (1647)

The profound effect of emotion on memory storage was recognized long before the days of Descartes. In fact, it was said that throwing a child into a river after witnessing an important event, such as a wedding or granting of land to a township, was a medieval method for encouraging a lasting memory of the occasion (McGaugh, 2003). Considerable attention has been devoted to understanding the impact of emotional arousal on brain systems that store new experiences into long-term memory. Emotional arousal serves an important role in memory processing by first initiating attentional (Revelle and Loftus, 1992, Walker, 1958) and metabolic (Ekman et al., 1983, Witvliet and Vrana, 1995) resources that permit organisms to adapt rapidly to environmental challenges. Physiological changes recruited to mobilize resources for immediate responses also serve a second crucial function. They modulate brain processes to ensure that significant experiences are stored effectively into long-term memory. Thus, emotional arousal serves an important adaptive role in initiating rapid responses to momentary fluctuations in environmental conditions, and in regulating neural representations of these changes. This review discusses experimental approaches and relevant findings that provide the foundation for current understanding of coordinated interactions between arousal activated peripheral hormones and brain processes that modulate memory formation.

Section snippets

Effects of arousal on peripheral hormones and central norepinephrine

Emotional arousal produced by aversive stressors or highly rewarding events results in the release of epinephrine (adrenalin) and glucocorticoids (cortisol; corticosterone in rats) from the adrenal glands (Roozendaal et al., 2009a). Drugs and other treatments that increase concentrations of epinephrine or glucocorticoids during, or following, learning enhance memory in rats and mice (Gold and van Buskirk, 1978, Introini-Collison et al., 1992, Jurado-Berbel et al., 2010, King and Williams, 2009,

Pathways for conveying effects of arousal hormones on the brain

Findings indicating that amygdala norepinephrine levels are sensitive to epinephrine secretion provide strong evidence suggesting that emotion-induced secretion of epinephrine facilitates memory by direct actions on the amygdala. However, this implication is complicated by evidence that, even in highly stressful situations, epinephrine does not pass from the peripheral circulation into the brain (Arai et al., 1981, Pluta et al., 1994). As such, an understanding of how emotional arousal affects

The amygdala modulates memory consolidation by interacting with other brain regions

As discussed above, extensive evidence indicates that activation of the amygdala by stress hormones modulates the consolidation of emotionally arousing memories. It does not follow, however, that memory should be impaired by the loss of the amygdala, or that the amygdala is the site of storage of emotionally arousing memories. Inactivation of the amygdala prior to training or retention does not impair performance on a spatial water maze task, or a spatial win-shift or win-stay,

Synaptic mechanisms of amygdala modulation of long-term memory

As discussed above, considerable evidence indicates that amygdala modulation of memory consolidation involves influences on other brain regions, but little is known about the synaptic mechanisms of this interaction. One way to observe the effects of BLA activity on synaptic activity elsewhere in the brain is to measure expression of immediate early genes (IEGs) that are rapidly induced in response to synaptic activity. The IEG Arc (also Arg 3.1) is of particular interest as it appears to be a

Clinical relevance

The usefulness of all the passions consists in their strengthening and prolonging in the soul thoughts which are good for it to conserve… and all the harm they can do consists in their strengthening and conserving these thoughts more than is necessary

Descartes, The Passions of the Soul, (1647)

The knowledge garnered from the studies described above may contribute to the development of treatments for individuals suffering from memory and anxiety disorders. Firstly, it informs research designed

Conclusions

The amygdala is well-positioned to translate sympathetic arousal into synaptic plasticity that is distributed throughout the brain. A physiological mechanism to promote brain plasticity and rapid consolidation of memory for events that have a bearing on survival and well-being can have both adaptive and maladaptive implications. Here, we propose that the sympathetic “fight or flight” response goes beyond the peripheral nervous system by implementing epinephrine stimulation of the vagus nerve,

Acknowledgements

This work was supported by National Institute of Mental Health grants MH 12526-43 (JLM) and MH 086960-01A1 (CKM), and the National Science Foundation, through grant NSF-0720170 (CLW). CKM is also supported by MicroTransponder.

References (220)

  • H.D. Critchley et al.

    Fear conditioning in humans: the influence of awareness and autonomic arousal on functional neuroanatomy

    Neuron

    (2002)
  • N. Dahlgren et al.

    Cerebral functional, metabolic and circulatory effects of intravenous infusion of adrenaline in the rat

    Brain Res.

    (1980)
  • F. Dolcos et al.

    Interaction between the amygdala and the medial temporal lobe memory system predicts better memory for emotional events

    Neuron

    (2004)
  • B. Ferry et al.

    Clenbuterol administration into the basolateral amygdala post-training enhances retention in an inhibitory avoidance task

    Neurobiol. Learn. Mem.

    (1999)
  • B.H. Friedman

    An autonomic flexibility-neurovisceral integration model of anxiety and cardiac vagal tone

    Biol. Psychol.

    (2007)
  • R. Galvez et al.

    Norepinephrine release in the amygdala in response to footshock stimulation

    Neurobiol. Learn. Mem.

    (1996)
  • P.E. Gold et al.

    Posttraining brain norepinephrine concentrations: correlation with retention performance of avoidance training and with peripheral epinephrine modulation of memory processing

    Behav. Biol.

    (1978)
  • A.R. Granata et al.

    Release of [3H]l-glutamine acid (l-Glu) and [3H]d-aspartic acid (d-Asp) in the area of nucleus tractus solitarius in vivo produced by stimulation of the vagus nerve

    Brain Res.

    (1983)
  • D.A. Groves et al.

    Recordings from the rat locus coeruleus during acute vagal nerve stimulation in the anaesthetised rat

    Neurosci. Lett.

    (2005)
  • T. Hatfield et al.

    Norepinephrine infused into the basolateral amygdala posttraining enhances retention in a spatial water maze task

    Neurobiol. Learn. Mem.

    (1999)
  • R.N. Holdefer et al.

    The effects of peripheral d-amphetamine, 4-OH amphetamine, and epinephrine on maintained discharge in the locus coeruleus with reference to the modulation of learning and memory by these substances

    Brain Res.

    (1987)
  • C.M. Holloway et al.

    Post-training disruption of Arc protein expression in the anterior cingulate cortex impairs long-term memory for inhibitory avoidance training

    Neurobiol. Learn. Mem.

    (2011)
  • H. Hu et al.

    Emotion enhances learning via norepinephrine regulation of AMPA-receptor trafficking

    Cell

    (2007)
  • Y. Ikegaya et al.

    High-frequency stimulation of the basolateral amygdala facilitates the induction of long-term potentiation in the dentate gyrus in vivo

    Neurosci. Res.

    (1995)
  • I.B. Introini et al.

    Pharmacological evidence of a central effect of naltrexone, morphine, and beta-endorphin and a peripheral effect of met- and leu-enkephalin on retention of an inhibitory response in mice

    Behav. Neural Biol.

    (1985)
  • I. Introini-Collison et al.

    Memory-enhancing effects of post-training dipivefrin and epinephrine: involvement of peripheral and central adrenergic receptors

    Brain Res.

    (1992)
  • E. Jodo et al.

    Activation of locus coeruleus by prefrontal cortex is mediated by excitatory amino acid inputs

    Brain Res.

    (1997)
  • P. Jurado-Berbel et al.

    Standard object recognition memory and “what” and “where” components: Improvement by post-training epinephrine in highly habituated rats

    Behav. Brain Res.

    (2010)
  • E.C. Kerfoot et al.

    Functional interactions between the nucleus tractus solitarius (NTS) and nucleus accumbens shell in modulating memory for arousing experiences

    Neurobiol. Learn. Mem.

    (2008)
  • L. Kilpatrick et al.

    Amygdala modulation of parahippocampal and frontal regions during emotionally influenced memory storage

    Neuroimage

    (2003)
  • K.C. Liang et al.

    Modulating effects of posttraining epinephrine on memory: involvement of the amygdala noradrenergic system

    Brain Res.

    (1986)
  • K.C. Liang et al.

    Lesions of the stria terminalis attenuate the amnestic effect of amygdaloid stimulation on avoidance responses

    Brain Res.

    (1983)
  • A. Aerni et al.

    Low-dose cortisol for symptoms of posttraumatic stress disorder

    Am. J. Psychiatry

    (2004)
  • R.E. Allchin et al.

    Electrical stimulation of the vagus increases extracellular glutamate recovered from the nucleus tractus solitarii of the cat by in vivo microdialysis

    Exp. Physiol.

    (1994)
  • A.K. Anderson et al.

    Emotional memories are not all created equal: evidence for selective memory enhancement

    Learn. Mem.

    (2006)
  • M.C. Andresen et al.

    Non-NMDA receptors mediate sensory afferent synaptic transmission in medial nucleus tractus solitarius

    Am. J. Physiol.

    (1990)
  • T. Arai et al.

    Blood–brain barrier impairment after cardiac resuscitation

    Crit. Care Med.

    (1981)
  • E. Asan

    The catecholaminergic innervation of the rat amygdala

    Adv. Anat. Embryol. Cell Biol.

    (1998)
  • F. Ballarini et al.

    Behavioral tagging is a general mechanism of long-term memory formation

    Proc. Natl. Acad. Sci. U.S.A.

    (2009)
  • G.G. Berntson et al.

    Ascending visceral regulation of cortical affective information processing

    Eur. J. Neurosci.

    (2003)
  • L. Bevilaqua et al.

    Agents that affect cAMP levels or protein kinase A activity modulate memory consolidation when injected into rat hippocampus but not amygdala

    Braz. J. Med. Biol. Res.

    (1997)
  • S. Borson et al.

    Impaired sympathetic nervous system response to cognitive effort in early Alzheimer's disease

    J. Gerontol.

    (1989)
  • L. Cahill et al.

    The amygdala and emotional memory

    Nature

    (1995)
  • L. Cahill et al.

    Amygdala activity at encoding correlated with long-term, free recall of emotional information

    Proc. Natl. Acad. Sci. U.S.A.

    (1996)
  • L. Cahill et al.

    Beta-adrenergic activation and memory for emotional events

    Nature

    (1994)
  • W.H. Cai et al.

    Postreactivation glucocorticoids impair recall of established fear memory

    J. Neurosci.

    (2006)
  • T. Canli et al.

    Event-related activation in the human amygdala associates with later memory for individual emotional experience

    J. Neurosci.

    (2000)
  • J.M. Cedarbaum et al.

    Afferent projections to the rat locus coeruleus as determined by a retrograde tracing technique

    J. Comp. Neurol.

    (1978)
  • R.T. Chatterton et al.

    Salivary alpha-amylase as a measure of endogenous adrenergic activity

    Clin. Physiol.

    (1996)
  • K.B. Clark et al.

    Enhanced recognition memory following vagus nerve stimulation in human subjects

    Nat. Neurosci.

    (1999)
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