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

Stefan Herlitze, Katharina Spoida

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?
Pauline Bohne

Pauline Bohne

Doktorandin A07

Ruhr-Universität Bochum

Stefan Herlitze

Stefan Herlitze

Projektleiter A07

Ruhr-Universität Bochum

Katharina Spoida

Katharina Spoida

Projektleiterin A07

Ruhr-Universität Bochum

Sandra Süß

Sandra Süß

Doktorandin A07

Ruhr-Universität Bochum

10 project-relevant publications

Armbruster BN, Li X, Pausch MH, Herlitze S, Roth BL (2007) Evolving the lock to fit the key to create a family of G protein-coupled receptors potently activated by an inert ligand. Proc Natl Acad Sci USA. 104(12): 5163–5168.

Gutierrez DV, Mark MD, Masseck O, Maejima T, Kuckelsberg D, Hyde RA, Krause M, Kruse W, Herlitze S (2011) Optogenetic control of motor coordination by Gi/o protein-coupled vertebrate rhodopsin in cerebellar Purkinje cells. J Biol Chem. 286(29): 25848–25858.

Li X, Gutierrez DV, Hanson MG, Han J, Mark MD, Chiel H, Hegemann P, Landmesser LT, Herlitze S (2005) Fast noninvasive activation and inhibition of neural and network activity by vertebrate rhodopsin and green algae channelrhodopsin. Proc Natl Acad Sci USA. 102(49): 17816–17821.

Liu C, Maejima T, Wyler SC, Casadesus G, Herlitze S, Deneris ES (2010) Pet-1 is required across different stages of life to regulate serotonergic function. Nat Neurosci. 13(10): 1190–1198.

Lux V, Masseck OA, Herlitze S, Sauvage MM (2015) Optogenetic Destabilization of the Memory Trace in CA1: Insights into Reconsolidation and Retrieval Processes. Cereb Cortex.

Masseck OA, Spoida K, Dalkara D, Maejima T, Rubelowski JM, Wallhorn L, Deneris ES, Herlitze S (2014) Vertebrate cone opsins enable sustained and highly sensitive rapid control of Gi/o signaling in anxiety circuitry. Neuron. 81(6): 1263–1273.

Oh E, Maejima T, Liu C, Deneris E, Herlitze S (2010) Substitution of 5-HT1A receptor signaling by a light-activated G protein-coupled receptor. J Biol Chem. 285(40): 30825–30836.

Scott MM, Wylie CJ, Lerch JK, Murphy R, Lobur K, Herlitze S, Jiang W, Conlon RA, Strowbridge BW, Deneris ES (2005) A genetic approach to access serotonin neurons for in vivo and in vitro studies. Proc Natl Acad Sci USA. 102(45): 16472–16477.

Spoida K, Eickelbeck D, Karapinar R, Eckhardt T, Mark MD, Jancke D, Ehinger BV, Konig P, Dalkara D, Herlitze S, Masseck OA (2016) Melanopsin Variants as Intrinsic Optogenetic On and Off Switches for Transient versus Sustained Activation of G Protein Pathways. Curr Biol. 26(9): 1206–1212.

Spoida K, Masseck OA, Deneris ES, Herlitze S (2014) Gq/5-HT2c receptor signals activate a local GABAergic inhibitory feedback circuit to modulate serotonergic firing and anxiety in mice. Proc Natl Acad Sci USA. 111(17): 6479– 6484.