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Much evidence suggests that variation in expression of the 5-hydroxytryptamine (5-HT) transporter (5-HTT) is linked to risk of psychiatric illness, but the neurobiological basis of this association is uncertain. In this study, we investigated the impact of variation in 5-HTT expression on subsecond fluctuations in extracellular 5-HT concentrations ([5-HT](o) ). Stimulus-evoked [5-HT](o) was detected using fast-scan cyclic voltammetry at carbon-fibre microelectrodes in the substantia nigra in brain slices from 5-HTT knockout (KO) and 5-HTT over-expressing (OE) mice. Compared with wild-type (WT) controls, evoked [5-HT](o) was greater in KO and less in OE mice. In WT controls, evoked [5-HT](o) was frequency-sensitive; however, in both KO and OE mice, evoked [5-HT](o) showed a striking loss of frequency sensitivity. The latter was observed in WT mice after application of a 5-HTT blocker. These data show that while variation in 5-HTT expression modified the peak magnitude of [5-HT](o) evoked by any given stimulus in a gene dose dependent manner, there was a non-linear relationship between 5-HTT expression and frequency sensitivity. Overall, the findings suggest that variation in 5-HTT expression has a marked effect on frequency sensitivity which is a fundamental property of normal 5-HT transmission.

Original publication

DOI

10.1111/j.1471-4159.2010.07001.x

Type

Journal article

Journal

J Neurochem

Publication Date

11/2010

Volume

115

Pages

965 - 973

Keywords

Animals, Gene Expression Regulation, Male, Mice, Mice, Inbred C57BL, Mice, Knockout, Mice, Transgenic, Models, Genetic, Nonlinear Dynamics, Serotonin, Serotonin Plasma Membrane Transport Proteins, Signal Transduction, Time Factors