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Lookup NU author(s): Dr Marco BocchioORCiD
This is the authors' accepted manuscript of an article that has been published in its final definitive form by Nature, 2015.
For re-use rights please refer to the publisher's terms and conditions.
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 post-traumatic 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 interneuron 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 due to reduced 5-HT2A function and not to 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.Neuropsychopharmacology accepted article preview online, 08 June 2015. doi:10.1038/npp.2015.157.
Author(s): Bocchio M, Fucsina G, Oikonomidis L, McHugh SB, Bannerman DM, Sharp T, Capogna M
Publication type: Article
Publication status: Published
Journal: Neuropsychopharmacology
Year: 2015
Volume: 40
Issue: 13
Pages: 3015-3026
Online publication date: 08/06/2015
Acceptance date: 26/05/2015
Date deposited: 07/05/2021
ISSN (electronic): 1740-634X
Publisher: Nature
URL: https://doi.org/10.1038/npp.2015.157
DOI: 10.1038/npp.2015.157
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