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A07 – Interaction between stress and serotonergic signalling pathways to modulate extinction learning in the amygdala

Katharina Spoida, Stefan Herlitze

The amygdala has been identified as one of the main neuronal circuits involved in the processing of memories of emotional behavior including anxiety and fear and is one of the key components in the brain for processing stress responses. Thus, we will investigate the role of serotonergic signaling pathways within the amygdala for aversive learning and extinction under normal and stress conditions. Using an optogenetic strategy we will first control serotonin release directly in the amygdala and then 5HT2A and 5HT2C receptor pathways in specifically in GABAergic or glutamtergic neurons to enhance or inhibit fear conditioning, extinction, renewal and reinstatement under normal and stress conditions.

Guiding questions of A07:

  • How does serotonin release in the amygdala in vivo affect fear conditioning, extinction, renewal and reinstatement under normal and stress conditions?
  • How do 5HT2A and 5HT2C receptor signals activated either in GABAergic (parvalbumin positive) or glutamatergic neurons in the basolateral amygdala, respectively, enhance or inhibit fear conditioning, extinction, renewal and reinstatement under normal and stress conditions?
  • How do 5HT2A and 5HT2C receptor signals in either GABAergic (parvalbumin positive) or glutamatergic neurons in the basolateral amygdala determine the cellular responses of GABAergic and glutamatergic neurons during fear conditioning and extinction under normal and stress conditions?
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Katharina Spoida

Projektleiterin A07

Ruhr-Universität Bochum

Stefan Herlitze

Projektleiter A07

Ruhr-Universität Bochum

Hanna Böke

Doktorandin A07

Ruhr-Universität Bochum

Lennard Rohr

Doktorand A07

Ruhr-Universität Bochum

10 project-relevant publications

Barzan R, Bozkurt B, Nejad MM, Süß ST, Surdin T, Böke H, Spoida K, Azimi Z, Grömmke M, Eickelbeck D, Mark MD, Rohr L, Siveke I, Cheng S, Herlitze S, Jancke D (2024) Gain control of sensory input across polysynaptic circuitries in mouse visual cortex by a single G protein-coupled receptor type (5-HT2A). Nat Commun 15:8078.https://doi.org/10.1038/s41467-024-51861-1 

Bihorac J, Salem Y, Lückemann L, Schedlowski M, Doenlen R, Engler H, Mark MD, Dombrowski K, Spoida K, Hadamitzky M (2024) Investigations on the Ability of the Insular Cortex to Process Peripheral Immunosuppression. J Neuroimmune Pharmacol 19:40.https://doi.org/10.1007/s11481-024-10143-9 

Ito K, Sato K, Tsuneoka Y, Maejima T, Okuno H, Hamasaki Y, Murakawa S, Takabayashi Y, Yoshihara C, Shindo S, Uki H, Herlitze S, Seki M, Suzuki Y, Sakurai T, Kuroda KO, Minami M, Amano T (2023) Synaptic plasticity in the medial preoptic area of male mice encodes social experiences with female and regulates behavior toward young. bioRxiv:2023.10.23.560098.https://doi.org/10.1101/2023.10.23.560098 

Karapinar R, Schwitalla JC, Eickelbeck D, Pakusch J, Mücher B, Grömmke M, Surdin T, Knöpfel T, Mark MD, Siveke I, Herlitze S (2021) Reverse optogenetics of G protein signaling by zebrafish non-visual opsin Opn7b for synchronization of neuronal networks. Nat Commun 12:4488.https://doi.org/10.1038/s41467-021-24718-0 

Mücher B, Garrido-Charles A, Cyganek L, Bruegmann T, Dalkara D, Siveke I, Herlitze S (2025) Guiding G protein signaling by target enhancement of GPCRs. bioRxiv:2025.02.06.636923.https://doi.org/10.1101/2025.02.06.636923 

Rook N, Tuff JM, Isparta S, Masseck OA, Herlitze S, Güntürkün O, Pusch R (2021) AAV1 is the optimal viral vector for optogenetic experiments in pigeons (Columba livia). Commun Biol 4:100.https://doi.org/10.1038/s42003-020-01595-9 

Schulte H, Böke H, Lössl P, Worm M, Siveke I, Herlitze S, Spoida K (2025) Chemogenetic modulation of CRF neurons in the BNST compensates for phenotypic behavioral differences in fear extinction learning of 5-HT2C receptor mutant mice. Research Square https://doi.org/10.21203/rs.3.rs-5604701/v1 

Surdin T, Grömmke M, Böke H, Barcik M, Azimi Z, Jancke D, Herlitze S, Mark M, Siveke I (2022) Optogenetic control of mGluR1 signaling modulates synaptic plasticity and cerebellum driven learning.https://doi.org/10.1016/j.isci.2022.105828 

Süß ST, Olbricht LM, Herlitze S, Spoida K (2022) Constitutive 5-HT2C receptor knock-out facilitates fear extinction through altered activity of a dorsal raphe-bed nucleus of the stria terminalis pathway. Transl Psychiatry 12:487.https://doi.org/10.1038/s41398-022-02252-x 

Tuff, J., Haselhuhn, K., Surdin, T., Herlitze, S., Ziegler, M., Güntürkün, O., & Rook, N. (2025) Achieving cell-type specific transduction with adeno-associated viral vectors in pigeons. bioRxiv 2025.04.29.651184 https://doi.org/10.1101/2025.04.29.651184