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Erasing Fear: Effect of Disrupting Fear Memory Reconsolidation on Central and Peripheral Nervous System Activity
Uppsala University, Disciplinary Domain of Humanities and Social Sciences, Faculty of Social Sciences, Department of Psychology.
2012 (English)Doctoral thesis, comprehensive summary (Other academic)
Abstract [en]

Fear memories, here defined as learned associations between a stimulus and a physiological fear reaction, are formed through fear conditioning. In animals, fear memories, present in the lateral amygdala, undergo reconsolidation after recall. Moreover, this reconsolidation process can be disrupted both pharmacologically and behaviourally, resulting in a reduced fear response to the stimulus. This thesis examines the attenuation of fear memories by disrupting reconsolidation in humans, using measures of both the central and peripheral nervous system activity. Serotonergic and dopaminergic genes have previously been tied to both fear conditioning and anxiety disorders, where fear conditioning mechanisms are important. In order to evaluate the possible role of fear memory reconsolidation mechanims in the effect on fear and anxiety by these genes, this thesis also compare the reconsolidation disruption effect between different serotonergic and dopaminergic genotypes.

Study I examined the attentuation of fear memories by disrupting reconsolidation in humans using reacquisition as a measure of the return of fear. Moreover, study I investigated the impact of differences in serotonergic and dopaminergic alleles on this process.

Study II examined the attentuation of fear memories by disrupting reconsolidation in humans using reinstatement as a measure of the return of fear. Study II also investigated the impact of differences in serotonergic and dopaminergic alleles on the process of fear memory reconsolidation.

Study III used psychophysiology and fMRI to localize the functional neural activity mediating the fear memory reconsolidation disruption effect.

In summary, this thesis provides evidence that fear memories are attenuated by reconsolidation disruption in humans and that serotonergic and dopaminergic alleles influence this process. Moreover, this thesis support that human fear memory reconsolidation is amygdala-dependent, suggesting an evolutionary shared memory mechanism.

Place, publisher, year, edition, pages
Uppsala: Acta Universitatis Upsaliensis, 2012. , 62 p.
Series
Digital Comprehensive Summaries of Uppsala Dissertations from the Faculty of Social Sciences, ISSN 1652-9030 ; 81
Keyword [en]
Memory reconsolidation; fear conditioning; serotonin; dopamine; polymorphism; gene; exposure therapy; fMRI; amygdala
National Category
Psychology
Identifiers
URN: urn:nbn:se:uu:diva-180202ISBN: 978-91-554-8455-2 (print)OAI: oai:DiVA.org:uu-180202DiVA: diva2:548772
Public defence
2012-10-12, Universitetshuset, Sal IX, Biskopsgatan 3, Uppsala, 13:15 (Swedish)
Supervisors
Funder
Swedish Research Council
Available from: 2012-09-21 Created: 2012-08-31 Last updated: 2013-01-23Bibliographically approved
List of papers
1. Human fear reconsolidation and allelic differences in serotonergic and dopaminergic genes
Open this publication in new window or tab >>Human fear reconsolidation and allelic differences in serotonergic and dopaminergic genes
2012 (English)In: Translational Psychiatry, ISSN 2158-3188, E-ISSN 2158-3188, Vol. 2, e76Article in journal (Refereed) Published
Abstract [en]

Fear memory persistence, central for the development and maintenance of anxiety disorders, is partially genetically controlled. Recently, consolidation and reconsolidation processes have been reported to affect fear memory stability and integrity. This study explored the impact of reconsolidation processes and genetic make-up on fear reacquisition by manipulating reconsolidation using extinction performed outside or inside a reconsolidation interval. Reacquisition measured by skin conductance responses was stronger in individuals that extinguished outside (6 h) than inside (10 min) the reconsolidation interval. However, the effect was predominantly present in val/val homozygotes of the functional val158met polymorphism of the Catechol O-methyltransferase (COMT) enzyme and in short allele carriers of the serotonin transporter length 5-HTTLPR polymorphism. These results demonstrate that reconsolidation of human fear memory is influenced by dopamine and serotonin related genes.

Place, publisher, year, edition, pages
Macmillan Publishers Ltd., 2012
Keyword
dopamine, fear conditioning, genes, memory reconsolidation, polymorphism, serotonin
National Category
Psychology
Identifiers
urn:nbn:se:uu:diva-180177 (URN)10.1038/tp.2012.5 (DOI)000315989800001 ()22832813 (PubMedID)
Funder
Swedish Research CouncilForte, Swedish Research Council for Health, Working Life and Welfare
Available from: 2012-08-31 Created: 2012-08-31 Last updated: 2017-12-07Bibliographically approved
2. Serotonergic and dopaminergic modulation of the prevention of return of fear using reconsolidation.
Open this publication in new window or tab >>Serotonergic and dopaminergic modulation of the prevention of return of fear using reconsolidation.
(English)Manuscript (preprint) (Other academic)
Abstract [en]

Disruption of fear reconsolidation results in permanent memory suppression in fear conditioning protocols in animals and humans. Serotonergic and dopaminergic polymorphisms have been associated to this process. Specifically, reacquisition of fear after disrupted reconsolidation was compromised in human short alle carriers of the serotonin transporter gene linked polymorphic region (5-HTTLPR) and in val/val homozygotes of the val158met catechol-O-methyltransferease (COMT) functional polymorphisms. The present study examined if the gene effects similarly would impact reinstatement, another measure reflecting return of fear, following unpaired shock presentations. Skin conductance responses served as the measure of acquisition, extinction and return of fear. During the reinstatement session return of fear tended to be stronger in in val/val homozygotes of the COMT polymorphism who extinguished outside (6 h) as compared to inside (10 min) the reconsolidation interval following a memory reminder. Carriers of the short allele of the 5-HTTLPR polymorphism displayed a similar pattern in response to the previously shock associated cue. These results partially replicate for reinstatement the gene effect demonstrated previously for reacquisition, but fail to conceptually replicate the main effect averaged over all genotypes. Collectively, data support that reconsolidation of human fear memory is influenced by dopaminergic and serotonergic genes.

Keyword
Memory reconsolidation; fear conditioning; cold pressor test; serotonin; dopamine; polymorphism; genes
National Category
Psychology
Identifiers
urn:nbn:se:uu:diva-180200 (URN)
Funder
Swedish Research CouncilFAS, Swedish Council for Working Life and Social Research
Available from: 2012-08-31 Created: 2012-08-31 Last updated: 2013-01-23
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