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Neuropsychopharmacology. 2015 Dec;40(13):3015-26. doi: 10.1038/npp.2015.157. Epub 2015 Jun 8.

Increased Serotonin Transporter Expression Reduces Fear and Recruitment of Parvalbumin Interneurons of the Amygdala.

Author information

1
MRC Brain Network Dynamics Unit, Department of Pharmacology, University of Oxford, Oxford, UK.
2
Department of Pharmacology, University of Oxford, Oxford, UK.
3
Department of Experimental Psychology, University of Oxford, Oxford, UK.

Abstract

Genetic association studies suggest that variations in the 5-hydroxytryptamine (5-HT; serotonin) transporter (5-HTT) gene are associated with susceptibility to psychiatric disorders such as anxiety or posttraumatic stress disorder. Individuals carrying high 5-HTT-expressing gene variants display low amygdala reactivity to fearful stimuli. Mice overexpressing the 5-HTT (5-HTTOE), an animal model of this human variation, show impaired fear, together with reduced fear-evoked theta oscillations in the basolateral amygdala (BLA). However, it is unclear how variation in 5-HTT gene expression impacts on the microcircuitry of the BLA to change behavior. We addressed this issue by investigating the activity of parvalbumin (PV)-expressing interneurons (PVINs), the biggest IN population in the basal amygdala (BA). We found that increased 5-HTT expression impairs the recruitment of PVINs (measured by their c-Fos immunoreactivity) during fear. Ex vivo patch-clamp recordings demonstrated that the depolarizing effect of 5-HT on PVINs was mediated by 5-HT2A receptor. In 5-HTTOE mice, 5-HT-evoked depolarization of PVINs and synaptic inhibition of principal cells, which provide the major output of the BA, were impaired. This deficit was because of reduced 5-HT2A function and not because of increased 5-HT uptake. Collectively, these findings provide novel cellular mechanisms that are likely to contribute to differences in emotional behaviors linked with genetic variations of the 5-HTT.

PMID:
26052039
PMCID:
PMC4864439
DOI:
10.1038/npp.2015.157
[Indexed for MEDLINE]
Free PMC Article
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