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ADRA2B genotype differentially modulates stress-induced neural activity in the amygdala and hippocampus during emotional memory retrieval

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Abstract

Rationale

Noradrenaline interacts with stress hormones in the amygdala and hippocampus to enhance emotional memory consolidation, but the noradrenergic-glucocorticoid interaction at retrieval, where stress impairs memory, is less understood.

Objectives

We used a genetic neuroimaging approach to investigate whether a genetic variation of the noradrenergic system impacts stress-induced neural activity in amygdala and hippocampus during recognition of emotional memory.

Methods

This study is based on genotype-dependent reanalysis of data from our previous publication (Li et al. Brain Imaging Behav 2014). Twenty-two healthy male volunteers were genotyped for the ADRA2B gene encoding the α2B-adrenergic receptor. Ten deletion carriers and 12 noncarriers performed an emotional face recognition task, while their brain activity was measured with fMRI. During encoding, 50 fearful and 50 neutral faces were presented. One hour later, they underwent either an acute stress (Trier Social Stress Test) or a control procedure which was followed immediately by the retrieval session, where participants had to discriminate between 100 old and 50 new faces.

Results

A genotype-dependent modulation of neural activity at retrieval was found in the bilateral amygdala and right hippocampus. Deletion carriers showed decreased neural activity in the amygdala when recognizing emotional faces in control condition and increased amygdala activity under stress. Noncarriers showed no differences in emotional modulated amygdala activation under stress or control. Instead, stress-induced increases during recognition of emotional faces were present in the right hippocampus.

Conclusion

The genotype-dependent effects of acute stress on neural activity in amygdala and hippocampus provide evidence for noradrenergic-glucocorticoid interaction in emotional memory retrieval.

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Abbreviations

fMRI:

Functional magnetic resonance imaging

BOLD:

Blood oxygenation level dependent

BMI:

Body mass index

TSST:

Trier Social Stress Test

ISI:

Inter-stimulus-interval

MDBF:

Multidimensional Mood State Questionnaire

EPI:

Echo planar imaging

TR:

Time to repeat

TE:

Time to echo

MPRAGE:

Magnetization prepared rapid acquisition gradient echo

FWHM:

Full-width-half-maximum

HRF:

Hemodynamic response function

FWE:

Family-wise error

ROIs:

Regions of interest

IPC:

Inferior parietal cortex

NA/A:

Noradrenaline and adrenaline

PTSD:

Posttraumatic stress disorder

LTL:

Left temporal lobectomy

RTL:

Right temporal lobectomy

References

  • Buchanan TW (2007) Retrieval of emotional memories. Psychol Bull 133:761–779

    Article  PubMed Central  PubMed  Google Scholar 

  • Buchanan TW, Tranel D, Adolphs R (2006) Memories for emotional autobiographical events following unilateral damage to medial temporal lobe. Brain 129:115–127

    Article  PubMed  Google Scholar 

  • Cousijn H, Rijpkema M, Qin S, van Marle HJ, Franke B, Hermans EJ, van Wingen G, Fernandez G (2010) Acute stress modulates genotype effects on amygdala processing in humans. Proc Natl Acad Sci U S A 107:9867–9872

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  • de Quervain DJ, Aerni A, Roozendaal B (2007a) Preventive effect of beta-adrenoceptor blockade on glucocorticoid-induced memory retrieval deficits. Am J Psychiatry 164:967–969

    Article  PubMed  Google Scholar 

  • de Quervain DJ, Kolassa IT, Ertl V, Onyut PL, Neuner F, Elbert T, Papassotiropoulos A (2007b) A deletion variant of the alpha2b-adrenoceptor is related to emotional memory in Europeans and Africans. Nat Neurosci 10:1137–1139

    Article  PubMed  Google Scholar 

  • Dickerson SS, Kemeny ME (2004) Acute stressors and cortisol responses: a theoretical integration and synthesis of laboratory research. Psychol Bull 130:355–391

    Article  PubMed  Google Scholar 

  • Dolcos F, LaBar KS, Cabeza R (2005) Remembering one year later: role of the amygdala and the medial temporal lobe memory system in retrieving emotional memories. Proc Natl Acad Sci U S A 102:2626–2631

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  • Frodl T, Moller HJ, Meisenzahl E (2008) Neuroimaging genetics: new perspectives in research on major depression? Acta Psychiatr Scand 118:363–372

    Article  CAS  PubMed  Google Scholar 

  • Fusar-Poli P, Placentino A, Carletti F, Landi P, Allen P, Surguladze S, Benedetti F, Abbamonte M, Gasparotti R, Barale F, Perez J, McGuire P, Politi P (2009) Functional atlas of emotional faces processing: a voxel-based meta-analysis of 105 functional magnetic resonance imaging studies. J Psychiatry Neurosci 34:418–432

    PubMed Central  PubMed  Google Scholar 

  • Henckens MJAG, van Wingen GA, Joëls M, Fernández G (2012) Time-dependent effects of cortisol on selective attention and emotional interference: a functional MRI study. Frontiers in Integrative Neuroscience 6

  • Hermans EJ, van Marle HJ, Ossewaarde L, Henckens MJ, Qin S, van Kesteren MT, Schoots VC, Cousijn H, Rijpkema M, Oostenveld R, Fernandez G (2011) Stress-related noradrenergic activity prompts large-scale neural network reconfiguration. Science 334:1151–1153

    Article  CAS  PubMed  Google Scholar 

  • Het S, Rohleder N, Schoofs D, Kirschbaum C, Wolf OT (2009) Neuroendocrine and psychometric evaluation of a placebo version of the ‘Trier Social Stress Test’. Psychoneuroendocrinology 34:1075–1086

    Article  CAS  PubMed  Google Scholar 

  • Kirschbaum C, Pirke KM, Hellhammer DH (1993) The ‘Trier Social Stress Test’—a tool for investigating psychobiological stress responses in a laboratory setting. Neuropsychobiology 28:76–81

    Article  CAS  PubMed  Google Scholar 

  • Koutroumani M, Daniilidou M, Giannakouros T, Proitsi P, Liapi D, Germanou A, Nikolakaki E, Tsolaki M (2013) The deletion variant of alpha2b-adrenergic receptor is associated with decreased risk in Alzheimer’s disease and mild cognitive impairment. J Neurol Sci 328:19–23

    Article  CAS  PubMed  Google Scholar 

  • Kroes MC, Strange BA, Dolan RJ (2010) Beta-adrenergic blockade during memory retrieval in humans evokes a sustained reduction of declarative emotional memory enhancement. J Neurosci 30:3959–3963

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  • Kukolja J, Schlapfer TE, Keysers C, Klingmuller D, Maier W, Fink GR, Hurlemann R (2008) Modeling a negative response bias in the human amygdala by noradrenergic-glucocorticoid interactions. J Neurosci 28:12868–12876

    Article  CAS  PubMed  Google Scholar 

  • Kukolja J, Klingmuller D, Maier W, Fink GR, Hurlemann R (2011) Noradrenergic-glucocorticoid modulation of emotional memory encoding in the human hippocampus. Psychol Med: 1–10

  • Li S, Weerda R, Guenzel F, Wolf OT, Thiel CM (2013) ADRA2B genotype modulates effects of acute psychosocial stress on emotional memory retrieval in healthy young men. Neurobiol Learn Mem 103:11–18

    Article  PubMed  Google Scholar 

  • Li S, Weerda R, Milde C, Wolf OT, Thiel CM (2014) Effects of acute psychosocial stress on neural activity to emotional and neutral faces in a face recognition memory paradigm. Brain Imaging Behav

  • Lupien SJ, Lepage M (2001) Stress, memory, and the hippocampus: can’t live with it, can’t live without it. Behav Brain Res 127:137–158

    Article  CAS  PubMed  Google Scholar 

  • Maldjian JA, Laurienti PJ, Kraft RA, Burdette JH (2003) An automated method for neuroanatomic and cytoarchitectonic atlas-based interrogation of fMRI data sets. Neuroimage 19:1233–1239

    Article  PubMed  Google Scholar 

  • McGaugh JL (2000) Memory--a century of consolidation. Science 287:248–251

  • McGaugh JL, Roozendaal B (2009) Drug enhancement of memory consolidation: historical perspective and neurobiological implications. Psychopharmacology (Berl) 202:3–14

    Article  CAS  Google Scholar 

  • McGaugh JL, Cahill L, Roozendaal B (1996) Involvement of the amygdala in memory storage: interaction with other brain systems. Proc Natl Acad Sci U S A 93:13508–13514

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  • Merz CJ, Wolf OT, Schweckendiek J, Klucken T, Vaitl D, Stark R (2013) Stress differentially affects fear conditioning in men and women. Psychoneuroendocrinology 38:2529–2541

    Article  PubMed  Google Scholar 

  • Murchison CF, Zhang XY, Zhang WP, Ouyang M, Lee A, Thomas SA (2004) A distinct role for norepinephrine in memory retrieval. Cell 117:131–143

    Article  CAS  PubMed  Google Scholar 

  • Rasch B, Spalek K, Buholzer S, Luechinger R, Boesiger P, Papassotiropoulos A, de Quervain DJ (2009) A genetic variation of the noradrenergic system is related to differential amygdala activation during encoding of emotional memories. Proc Natl Acad Sci U S A 106:19191–19196

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  • Rasch B, Papassotiropoulos A, de Quervain DF (2010) Imaging genetics of cognitive functions: focus on episodic memory. Neuroimage 53:870–877

    Article  CAS  PubMed  Google Scholar 

  • Roozendaal B, Griffith QK, Buranday J, De Quervain DJ, McGaugh JL (2003) The hippocampus mediates glucocorticoid-induced impairment of spatial memory retrieval: dependence on the basolateral amygdala. Proc Natl Acad Sci U S A 100:1328–1333

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  • Roozendaal B, Hahn EL, Nathan SV, de Quervain DJ, McGaugh JL (2004) Glucocorticoid effects on memory retrieval require concurrent noradrenergic activity in the hippocampus and basolateral amygdala. J Neurosci 24:8161–8169

    Article  CAS  PubMed  Google Scholar 

  • Roozendaal B, McEwen BS, Chattarji S (2009a) Stress, memory and the amygdala. Nat Rev Neurosci 10:423–433

    Article  CAS  PubMed  Google Scholar 

  • Roozendaal B, McReynolds JR, Van der Zee EA, Lee S, McGaugh JL, McIntyre CK (2009b) Glucocorticoid effects on memory consolidation depend on functional interactions between the medial prefrontal cortex and basolateral amygdala. J Neurosci 29:14299–14308

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  • Sara SJ (2009) The locus coeruleus and noradrenergic modulation of cognition. Nat Rev Neurosci 10:211–223

    Article  CAS  PubMed  Google Scholar 

  • Schwabe L, Romer S, Richter S, Dockendorf S, Bilak B, Schachinger H (2009) Stress effects on declarative memory retrieval are blocked by a beta-adrenoceptor antagonist in humans. Psychoneuroendocrinology 34:446–454

    Article  CAS  PubMed  Google Scholar 

  • Small KM, Brown KM, Forbes SL, Liggett SB (2001) Polymorphic deletion of three intracellular acidic residues of the alpha 2B-adrenergic receptor decreases G protein-coupled receptor kinase-mediated phosphorylation and desensitization. J Biol Chem 276:4917–4922

    Article  CAS  PubMed  Google Scholar 

  • Steyer R, Schwenkmezger P, Notz P, Eid M (1994) Der Mehrdimensionale Befindlichkeitsfragebogen (MDBF) (German). Diagnostica 40:320–328

  • Strange BA, Dolan RJ (2004) Beta-adrenergic modulation of emotional memory-evoked human amygdala and hippocampal responses. Proc Natl Acad Sci U S A 101:11454–11458

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  • Todd RM, Palombo DJ, Levine B, Anderson AK (2011) Genetic differences in emotionally enhanced memory. Neuropsychologia 49:734–744

    Article  PubMed  Google Scholar 

  • Todd RM, Muller DJ, Lee DH, Robertson A, Eaton T, Freeman N, Palombo DJ, Levine B, Anderson AK (2013a) Genes for emotion-enhanced remembering are linked to enhanced perceiving. Psychol Sci 24:2244–2253

    Article  PubMed  Google Scholar 

  • Todd RM, Muller DJ, Palombo DJ, Robertson A, Eaton T, Freeman N, Levine B, Anderson AK (2013b) Deletion variant in the ADRA2B gene increases coupling between emotional responses at encoding and later retrieval of emotional memories. Neurobiol Learn Mem

  • Urner M, van Wingen G, Franke B, Rijpkema M, Fernandez G, Tendolkar I (2011) Genetic variation of the alpha2b-adrenoceptor affects neural correlates of successful emotional memory formation. Hum Brain Mapp 32:2096–2103

    Article  PubMed  Google Scholar 

  • van Stegeren AH, Wolf OT, Everaerd W, Rombouts SA (2008) Interaction of endogenous cortisol and noradrenaline in the human amygdala. Prog Brain Res 167:263–268

    Article  PubMed  Google Scholar 

  • Walsh PS, Metzger DA, Higuchi R (1991) Chelex 100 as a medium for simple extraction of DNA for PCR-based typing from forensic material. Biotechniques 10:506–513

    CAS  PubMed  Google Scholar 

  • Wilker S, Elbert T, Kolassa IT (2013) The downside of strong emotional memories: how human memory-related genes influence the risk for posttraumatic stress disorder—a selective review. Neurobiol Learn Mem

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Acknowledgments

Shijia Li was supported by a scholarship from China Scholarship Council (CSC). Faces from Essex face database are downloaded from the website of Dr. Libor Spacek (http://cswww.essex.ac.uk/mv/allfaces/index.html) and faces from PICS database are downloaded from Psychological Image Collection at Stirling (http://pics.psych.stir.ac.uk/).

Conflict of interest

The authors have no conflict of interest to declare.

Author information

Authors and Affiliations

  1. Biological Psychology Lab, Department of Psychology, European Medical School, Carl von Ossietzky University, 26111, Oldenburg, Germany

    Shijia Li, Riklef Weerda, Christopher Milde & Christiane M. Thiel

  2. Research Center Neurosensory Science, Excellence Cluster Hearing4all, Carl von Ossietzky University, 26111, Oldenburg, Germany

    Christiane M. Thiel

  3. Cognitive Psychology, Institute of Cognitive Neuroscience, Ruhr-University Bochum, 44780, Bochum, Germany

    Oliver T. Wolf

  4. Clinical Affective Neuroimaging Laboratory (CANLAB), Center for Behavioral Brain Science, 39120, Magdeburg, Germany

    Shijia Li

  5. Department of Cognitive and Clinical Psychology, Central Institute of Mental Health, Medical Faculty Mannheim/Heidelberg University, 68159, Mannheim, Germany

    Christopher Milde

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  1. Shijia Li
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  2. Riklef Weerda
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  5. Christiane M. Thiel
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Correspondence to Shijia Li.

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Li, S., Weerda, R., Milde, C. et al. ADRA2B genotype differentially modulates stress-induced neural activity in the amygdala and hippocampus during emotional memory retrieval. Psychopharmacology 232, 755–764 (2015). https://doi.org/10.1007/s00213-014-3710-3

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  • DOI: https://doi.org/10.1007/s00213-014-3710-3

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