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| Item Type: | Article |
|---|---|
| Title: | Serotonin deficiency increases context-dependent fear learning through modulation of hippocampal activity |
| Creators Name: | Waider, J. and Popp, S. and Mlinar, B. and Montalbano, A. and Bonfiglio, F. and Aboagye, B. and Thuy, E. and Kern, R. and Thiel, C. and Araragi, N. and Svirin, E. and Schmitt-Böhrer, A.G. and Corradetti, R. and 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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