Barkus, Christopher and Line, Samantha J. and Huber, Anna and Capitao, Liliana and Lima, Joao and Jennings, Katie and Lowry, John P. and Sharp, Trevor and Bannerman, David M. and McHugh, Stephen B. (2014) Variation in Serotonin Transporter Expression Modulates FearEvoked Hemodynamic Responses and ThetaFrequency Neuronal Oscillations in the Amygdala. Biological Psychiatry, 75 (11). pp. 901-908. ISSN 0006-3223

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Abstract

Background Gene association studies detect an influence of natural variation in the 5-hydroxytryptamine transporter (5- HTT) gene on multiple aspects of individuality in brain function, ranging from personality traits through to susceptibility to psychiatric disorders such as anxiety and depression. The neural substrates of these associations are unknown. Human neuroimaging studies suggest modulation of the amygdala by 5-HTT variation, but this hypothesis is controversial and unresolved, and difficult to investigate further in humans. Methods We used a mouse model in which the 5-HTT is overexpressed throughout the brain and recorded hemodynamic responses (using a novel in vivo voltammetric monitoring method, analogous to blood oxygen level–dependent functional magnetic resonance imaging) and local field potentials during Pavlovian fear conditioning. Results Increased 5-HTT expression impaired, but did not prevent, fear learning and significantly reduced amygdala hemodynamic responses to aversive cues. Increased 5-HTT expression was also associated with reduced theta oscillations, which were a feature of aversive cue presentation in controls. Moreover, in control mice, but not those with high 5-HTT expression, there was a strong correlation between theta power and the amplitude of the hemodynamic response. Conclusions Direct experimental manipulation of 5-HTT expression levels throughout the brain markedly altered fear learning, amygdala hemodynamic responses, and neuronal oscillations.

Item Type:	Article
Additional Information:	The definitive version of this article is available at DOI: 10.1016/j.biopsych.2013.09.003
Keywords:	serotonin transporter; fMRI; amygdala; fear; tissue oxygen; theta oscillations;
Academic Unit:	Faculty of Science and Engineering > Chemistry
Item ID:	7004
Identification Number:	https://doi.org/10.1016/j.biopsych.2013.09.003
Depositing User:	John Lowry
Date Deposited:	03 Mar 2016 15:56
Journal or Publication Title:	Biological Psychiatry
Publisher:	Elsevier
Refereed:	Yes
Funders:	Wellcome Trust
URI:	http://www.sciencedirect.com/
Use Licence:	This item is available under a Creative Commons Attribution Non Commercial Share Alike Licence (CC BY-NC-SA). Details of this licence are available here

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