Cookies on this website

We use cookies to ensure that we give you the best experience on our website. If you click 'Accept all cookies' we'll assume that you are happy to receive all cookies and you won't see this message again. If you click 'Reject all non-essential cookies' only necessary cookies providing core functionality such as security, network management, and accessibility will be enabled. Click 'Find out more' for information on how to change your cookie settings.

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.

Original publication

DOI

10.1016/j.biopsych.2013.09.003

Type

Journal article

Journal

Biol Psychiatry

Publication Date

01/06/2014

Volume

75

Pages

901 - 908

Keywords

amygdala, fMRI, fear, serotonin transporter, theta oscillations, tissue oxygen, Amygdala, Animals, Fear, Male, Mice, Mice, Inbred C57BL, Neurons, Oxygen, Serotonin Plasma Membrane Transport Proteins, Theta Rhythm