Control and understanding of 5-HT1A/B signaling pathways and their involvement in anxiety behavior

• Applicant: Professorin Dr. Olivia Andrea Masseck
• Subject Area: Molecular Biology and Physiology of Neurons and Glial Cells
• Term: from 2012 to 2020
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 226458240

Serotonin (5-hydroxytryptamine; 5-HT) has been shown to modulate emotional behaviours and alterations in 5-HT levels have been related to different disease states including anxiety disorders. My proposal will investigate how changes in serotonergic signaling will lead to the development and manifestation of anxiety. (1) With the help of light activatable 5-HT1A and 5-HT1B receptors the autoregulation of the serotonergic system, which is mainly mediated by these two G-protein coupled receptors (GPCRs) will be investigated. Alterations in these two signaling pathways have been suggested to be responsible in the manifestation of anxiety. (2) Both 5-HT1 receptor chimeras will be expressed in GABAergic and pyramidal neuron of the medial prefrontal cortex (mPFC) to show in which way serotonergic neurotransmission within the mPFC is responsible for the development and manifestation of anxiety. (3) In addition, I will elucidate the plasticity changes of the 5-HT system during chronic light-activation of 5-HT1 signaling pathways and will investigate which anatomical and physiological changes occur. Modulation of 5-HT1 receptor pathways with high temporal and spatial resolution will lead to the understanding of how activation of these intracellular signaling pathways influence anxiety behavior and the manifestation and progression of the disease. My experiments and results will most likely contribute to the improvement of existing treatments and the development of new therapeutic strategies.

• DFG Programme: Research Grants