Journal article
Enhanced discriminative aversive learning and amygdala responsivity in 5-HT transporter mutant mice
- Abstract:
- Genetic variation in the human serotonin transporter (5-HTT) has been linked to altered fear learning but the data are inconsistent and the mechanism is unclear. The present study investigated conditioned aversive learning in 5-HTT knockout (KO) mice while simultaneously recording neural network activity (theta oscillations) and hemodynamic responses (tissue oxygen delivery) from the amygdala, a brain region necessary for forming fearful memories. Conditioned aversive learning was measured using a discrimination learning task in which one auditory cue was paired with foot-shock, whereas a second auditory cue was not. Compared with wild-type mice, 5-HTTKO mice exhibited faster discrimination learning. This effect was associated with stronger theta frequency oscillations and greater hemodynamic changes in the amygdala in response to both the emotionally relevant cues and the unconditioned foot-shock stimulus. Furthermore, hemodynamic responses to the unconditioned stimulus predicted behavioral discrimination performance the following day. Acute pharmacological 5-HTT blockade in wild-type mice produced a similar effect, to the extent that administration of citalopram during the fear conditioning sessions enhanced fear memory recall. Collectively, our data argue that loss of 5-HTT function enhances amygdala responsivity to aversive events and facilitates learning for emotionally relevant cues.
- Publication status:
- Published
- Peer review status:
- Peer reviewed
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(Preview, Version of record, pdf, 1.0MB, Terms of use)
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- Publisher copy:
- 10.1038/s41398-019-0476-8
Authors
- Publisher:
- Nature
- Journal:
- Translational psychiatry More from this journal
- Volume:
- 9
- Issue:
- 1
- Article number:
- 139
- Publication date:
- 2019-04-17
- Acceptance date:
- 2019-02-12
- DOI:
- ISSN:
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2158-3188
- Pmid:
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30996249
- Language:
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English
- Pubs id:
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pubs:993183
- UUID:
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uuid:6f9fb52c-b388-4bff-b4bd-48123f1b55d9
- Local pid:
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pubs:993183
- Source identifiers:
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993183
- Deposit date:
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2019-04-29
Terms of use
- Copyright holder:
- Lima et al
- Copyright date:
- 2019
- Notes:
- © The Author(s) 2019. This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/.
- Licence:
- CC Attribution (CC BY)
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