| First Author | Jennings KA | Year | 2010 |
| Journal | J Neurochem | Volume | 115 |
| Issue | 4 | Pages | 965-73 |
| PubMed ID | 20854367 | Mgi Jnum | J:166610 |
| Mgi Id | MGI:4848247 | Doi | 10.1111/j.1471-4159.2010.07001.x |
| Citation | Jennings KA, et al. (2010) Non-linear relationship between 5-HT transporter gene expression and frequency sensitivity of 5-HT signals. J Neurochem 115(4):965-73 |
| abstractText | 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. |
