Assoz.-Prof Dr. Ramon Tasan
Our research focusses on the integration of emotionally controlled survival circuits with a specific emphasis on how anxiety, fear and stress interacts with feeding and hunger. In particular, we are interested in the role of evolutionary conserved neuropeptides (e.g. Neuropeptide Y, Neurokinin B) in intrinsic circuitries within the extend amygdala as well as projections to hypothalamus and brain-stem (Comeras, Herzog, & Tasan, 2019). This will provide a deeper understanding of how feeding- and anxiety / fear-related circuitries mutually interact and integrate into a wider brain network. Our main findings include the identification of an evolutionary conserved reciprocal interaction of emotional and metabolic processes in the brain (Ip et al., 2019). Mechanistically, we demonstrated that hunger suppresses the consolidation of fear memories and facilitates the extinction of conditioned fear by modification of an amygdala microcircuit (Verma et al., 2016). Importantly, these findings are valid for several species, including human subjects. Thus, evolutionary conserved neuronal circuitries controlling feeding and hunger differentially integrate into those for anxiety and fear, under physiological conditions and upon dysregulation.
Focal points of interest
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Contribution of GABAergic neurons to the integration of emotional and metabolic behavior.
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Structural and functional cooperativity of co-localized neuropeptide modulators within GABAergic circuitries.
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Specific focus on neuropeptide expressing GABA neurons in amygdala-related circuitries, including central amygdala (CEA) and bed nucleus of the stria terminalis (BNST).
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Investigation of different neuronal clusters in the amygdala with region-dependent, sex-specific functional segregation and differential integration into cortical and hypothalamic circuitries.
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Identification of functionally defined neuronal ensembles of amygdala GABA neurons and their integration into excitatory circuitries to fine-tune adaptive behaviors in a sex-specific manner.
Technical proficiency and instrumentation
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Our laboratory performs a series of emotional and cognitive behavioral paradigms, including anxiety, fear (differential fear conditioning, fear extinction, pattern separation), and spatial learning tests in mice.
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We are integrating these data sets with long-term measurements of food intake and energy consumption in a metabolic phenotyping unit. This allows us to obtain real-time measurements of feeding / drinking and activity monitoring, with total activity, preferred location within the cage and wheel running, over several weeks and months. During these recordings, we apply restricted feeding paradigms, different diets and aversive learning tasks.
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For in vivo neuronal manipulations, we develop and employ AAV-mediated shRNA, CRISPR / saCas9, optogenetics / chemogenetics, reporter / activity sensors and genetically encoded cell-type-specific protein synthesis inhibition in transgenic mouse lines.
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We are running a viral vector platform for developing and packaging specifically designed constructs into different AAV pseudotypes with cell type preferring promoter / enhancer elements for permanent, recombinase-dependent, intersectional, and inducible expression systems.
Aspirations for the next 5 years
We propose to investigate the role of different neuropeptides, either individual or in combination, in the integration of feeding with anxiety / fear associated behavior in a cortical - extended amygdala -hypothalamic pathway. This will include genetic manipulation, activity monitoring, ex vivo electrophysiological recordings and expression profiling of specific BNST / CEA GABA neurons together with the investigation of their neuropeptide-dependent behavioral responses (emotional, metabolic, and cognitive). We want to uncover the underlying mechanism of differential regulation of these GABA neurons in males and females and their neuropeptide related contribution. We will focus on the BNST, which displays highly sexually diverse structural and functional composition and compare it to the closely related CEA, where responses are relatively equal between sexes.
References
- Comeras, L. B., Herzog, H., & Tasan, R. O. (2019). Neuropeptides at the crossroad of fear and hunger: a special focus on neuropeptide Y. Ann N Y Acad Sci, 1455(1), 59-80. doi:10.1111/nyas.14179
- Ip, C. K., Zhang, L., Farzi, A., Qi, Y., Clarke, I., Reed, F., Shi, Y. C., Enriquez, R., Dayas, C., Graham, B., Begg, D., Bruning, J. C., Lee, N. J., Hernandez-Sanchez, D., Gopalasingam, G., Koller, J., Tasan, R., Sperk, G., & Herzog, H. (2019). Amygdala NPY Circuits Promote the Development of Accelerated Obesity under Chronic Stress Conditions. Cell Metab, 30(1), 111-128 e116. doi:10.1016/j.cmet.2019.04.001
- Verma, D., Wood, J., Lach, G., Herzog, H., Sperk, G., & Tasan, R. (2016). Hunger Promotes Fear Extinction by Activation of an Amygdala Microcircuit. Neuropsychopharmacology, 41(2), 431-439. doi:10.1038/npp.2015.163
