Open AccessSERT and uncertainty: serotonin transporter expression influences information processing biases for ambiguous aversive cues in mice
Author(s) -
McHugh S. B.,
Barkus C.,
Lima J.,
Glover L. R.,
Sharp T.,
Bannerman D. M.
Publication year - 2015
Publication title -
genes, brain and behavior
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.315
H-Index - 91
eISSN - 1601-183X
pISSN - 1601-1848
DOI - 10.1111/gbb.12215
Subject(s) - serotonin transporter , psychology , serotonin plasma membrane transport proteins , serotonin , fear conditioning , cognition , neuroscience , aversive stimulus , expression (computer science) , biology , amygdala , genetics , receptor , computer science , programming language
The long allele variant of the serotonin transporter ( SERT , 5‐ HTT ) gene‐linked polymorphic region (5‐ HTTLPR ) is associated with higher levels of 5‐ HTT expression and reduced risk of developing affective disorders. However, little is known about the mechanisms underlying this protective effect. One hypothesis is that 5‐ HTT expression influences aversive information processing, with reduced negative cognitive bias present in those with higher 5‐ HTT expression. Here we investigated this hypothesis using genetically‐modified mice and a novel aversive learning paradigm. Mice with high levels of 5‐ HTT expression (5‐ HTT over‐expressing, 5‐ HTTOE mice) and wild‐type mice were trained to discriminate between three distinct auditory cues: one cue predicted footshock on all trials ( CS +); a second cue predicted the absence of footshock (CS−); and a third cue predicted footshock on 20% of trials ( CS20 %), and was therefore ambiguous. Wild‐type mice exhibited equivalently high levels of fear to the CS+ and CS20% and minimal fear to the CS−. In contrast, 5‐ HTTOE mice exhibited high levels of fear to the CS + but minimal fear to the CS− and the CS20 %. This selective reduction in fear to ambiguous aversive cues suggests that increased 5‐ HTT expression reduces negative cognitive bias for stimuli with uncertain outcomes.