GABAergic plasticity in neuronal circuits of fear

Vogel, Elisabeth. GABAergic plasticity in neuronal circuits of fear. 2015, Doctoral Thesis, University of Basel, Faculty of Science.

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Official URL: http://edoc.unibas.ch/diss/DissB_11669

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Neuronal circuits of fear and anxiety have been studied extensively not only to understand basic principles underlying anxiety disorders but also to investigate mechanisms of learning and memory. Fear conditioning is a powerful model system of associative learning, where the animal learns that an initially neutral stimulus predicts a fearful event. A key brain structure in this experimental paradigm is the amygdala, located in the temporal lobe. Synaptic plasticity of amygdala principle neurons gained a lot of attention and it has been shown how converging inputs trigger strengthening of synaptic transmission, which molecular changes are involved and which glutamatergic cell types and output pathways are important for high fear and low fear states. However, network mechanisms balancing the activity of these pyramidal neurons remain poorly understood. It is conceivable that amongst other contributors, local GABAergic interneurons might be involved and undergo plastic changes with fear conditioning and extinction.
In my thesis I focused on how GABAergic transmission onto pyramidal cells is organized in fear circuits. First, in a broad approach and in collaboration with Yu Kasugai and Franceso Ferraguti from the Medical University Innsbruck, we show that fear conditioning induces functional and ultrastructural changes at inhibitory synapses. Following fear learning, GABAergic transmission is enhanced, which is correlated with an enlargement of synapses and a change in receptor subunit composition.
Second, in target specific experiments, I studied the dynamic regulation of inhibition from CCK expressing interneurons onto two functionally distinct classes of projections neurons. Data indicate that characteristics at these synapses facilitate asymmetric activity of particular pyramidal cell populations via retrograde endocannabinoid signaling and that inhibitory control is organized in a cell type specific manner.
Advisors:Lüthi, Andreas and Bischofberger, Josef
Faculties and Departments:09 Associated Institutions > Friedrich Miescher Institut FMI > Neurobiology > Cellular mechanisms of learning and memory (Lüthi)
UniBasel Contributors:Bischofberger, Josef
Item Type:Thesis
Thesis Subtype:Doctoral Thesis
Thesis no:11669
Thesis status:Complete
Number of Pages:1 Online-Ressource (95 Seiten)
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Last Modified:22 Jan 2018 15:52
Deposited On:01 Sep 2016 08:05

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