Marco Capogna

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

Research output: Contribution to journal/Conference contribution in journal/Contribution to newspaperJournal articleResearchpeer-review

DOI

  • Marco Bocchio, MRC Brain Network Dynamics Unit, Department of Pharmacology, University of Oxford, Oxford OX1 3TH, UK; Department of Pharmacology, University of Oxford, Oxford OX1 3QT, UK.
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  • Giulia Fucsina, MRC Brain Network Dynamics Unit, Department of Pharmacology, University of Oxford, Oxford OX1 3TH, UK; Department of Pharmacology, University of Oxford, Oxford OX1 3QT, UK.
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  • Lydia Oikonomidis, University of Oxford, Department of Experimental Psychology, Tinbergen Building, Oxford, OX1 3UD, United Kingdom, +44 1865 271367.
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  • Stephen B McHugh, University of Oxford, Department of Experimental Psychology, Tinbergen Building, Oxford, OX1 3UD, United Kingdom, +44 1865 271367.
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  • David M Bannerman, University of Oxford, Department of Experimental Psychology, Tinbergen Building, Oxford, OX1 3UD, United Kingdom, +44 1865 271367.
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  • Trevor Sharp, Department of Pharmacology, University of Oxford, Oxford, UK
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  • Marco Capogna

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.

Original languageEnglish
JournalNeuropsychopharmacology
Volume40
Issue13
Pages (from-to)3015-26
Number of pages12
ISSN0893-133X
DOIs
Publication statusPublished - Dec 2015
Externally publishedYes

    Research areas

  • Action Potentials, Animals, Auditory Perception, Basolateral Nuclear Complex, Conditioning (Psychology), Electroshock, Fear, Female, Freezing Reaction, Cataleptic, Immunohistochemistry, Interneurons, Mice, Inbred C57BL, Mice, Inbred CBA, Mice, Transgenic, Neural Inhibition, Parvalbumins, Patch-Clamp Techniques, Proto-Oncogene Proteins c-fos, Receptor, Serotonin, 5-HT2A, Serotonin Plasma Membrane Transport Proteins, Tissue Culture Techniques, Journal Article, Research Support, Non-U.S. Gov't

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