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| Item Type: | Article |
|---|---|
| Title: | Serotonin deficiency increases context-dependent fear learning through modulation of hippocampal activity |
| Creators Name: | Waider, J., Popp, S., Mlinar, B., Montalbano, A., Bonfiglio, F., Aboagye, B., Thuy, E., Kern, R., Thiel, C., Araragi, N., Svirin, E., Schmitt-Böhrer, A.G., Corradetti, R., Lowry, C.A. and Lesch, K.P. |
| Abstract: | Brain serotonin (5-hydroxytryptamine, 5-HT) system dysfunction is implicated in exaggerated fear responses triggering various anxiety-, stress-, and trauma-related disorders. However, the underlying mechanisms are not well understood. Here, we investigated the impact of constitutively inactivated 5-HT synthesis on context-dependent fear learning and extinction using tryptophan hydroxylase 2 (Tph2) knockout mice. Fear conditioning and context-dependent fear memory extinction paradigms were combined with c-Fos imaging and electrophysiological recordings in the dorsal hippocampus (dHip). Tph2 mutant mice, completely devoid of 5-HT synthesis in brain, displayed accelerated fear memory formation and increased locomotor responses to foot shock. Furthermore, recall of context-dependent fear memory was increased. The behavioral responses were associated with increased c-Fos expression in the dHip and resistance to foot shock-induced impairment of hippocampal long-term potentiation (LTP). In conclusion, increased context-dependent fear memory resulting from brain 5-HT deficiency involves dysfunction of the hippocampal circuitry controlling contextual representation of fear-related behavioral responses. |
| Keywords: | Tryptophan Hydroxylase 2, Knockout, Fear Learning, Extinction, Long-Term Potentiation, Hippocampus, Immediate-Early Gene, Serotonin Deficiency, Animals, Mice |
| Source: | Frontiers in Neuroscience |
| ISSN: | 1662-453X |
| Publisher: | Frontiers Media SA |
| Volume: | 13 |
| Page Range: | 245 |
| Date: | April 2019 |
| Official Publication: | https://doi.org/10.3389/fnins.2019.00245 |
| PubMed: | View item in PubMed |
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