Univ.-Prof. Dr. Francesco Ferraguti
Our research group is based at the Institute of Pharmacology of the Medical University of Innsbruck. The laboratory is primarily interested in understanding the neural mechanisms mediating emotional information processing. We focus on the negative valence domain and on a macrocircuit involving the amygdala, ventral hippocampus and prefrontal cortex. Although a large body of in vivo work has suggested that fear and anxiety are encoded by largely overlapping, but also diverging networks, we explore how regional microcircuits contribute to these different emotional states. We take advantage of recent developments in molecular genetics, single cell recordings and photo-pharmacology to disentangle how specific changes in neuronal activity patterns result in the behavioural expression of fear or anxiety. The influence mediated by classical neurotransmitters (glutamate and GABA), neuropeptides and their receptors on negative emotional states is also a key research focus.
In addition, we investigate long-range connections between GABAergic neurons and cortical or subcortical brain structures as well as structural plasticity of GABAergic synapses.
Focal points of interest
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Whole-brain connectome of cortical GABAergic neurons.
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Neural circuit dynamics in the amygdala, ventral hippocampus and prefrontal cortex in relation to negative emotions (anxiety and fear), contribution of the GABAergic interneurons.
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Neuromodulation of GABAergic circuits/neurons.
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Synaptic plasticity (structural and functional) of GABAergic synapses.
Technical proficiency and instrumentation
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Our lab uses a large number of state-of-the-art behavioral paradigms to investigate negative emotions (anxiety and fear) in rodents.
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We apply in vivo optogenetics, photo-pharmacology and local field potential recordings from multiple brain areas to interrogate the role of specific neuronal classes/circuits in the negative valence domain.
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We routinely perform recordings of calcium transients in freely behaving mice using head-mounted miniscopes.
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We have extensive expertise in high-resolution microscopy including pre-embedding immunoelectron-microscopy and freeze-fracture replica immunolabelling.
Aspirations for the next 5 years
Our overarching aim is to elucidate how anxiety and fear arise form specific patterns of activity in distinct neurons of the amygdala-ventral hippocampus-prefrontal cortex macrocircuit. Moreover, we would like to understand which intrinsic GABAergic neurons contribute to the coding of these emotional states and how their neuroanatomical and pharmacological features may regulate the intensity of the emotion and in turn maladaptive states.
References
- Ramos-Prats A., Matulewicz P., Edenhofer M.L., Wang K-Y., Yeh C-W., Fajardo-Serrano A., Kress M., Kummer K., Lien C-C., Ferraguti F.* (2024) Loss of mGlu5 receptors in somatostatin-expressing neurons alters negative emotional states. Mol Psychiatry 29:2774-2786. doi: 10.1038/s41380-024-02541-5.
⇒ This study reveals a critical role of mGlu5 receptors on SST-expressing interneurons in regulating their excitability and in turn negative emotional states. - Ramos-Prats A., Paradiso E., Castaldi F., Sadeghi M, Mir M.Y., Hörtnagl H., Göbel G. and Ferraguti F.* (2022) VIP-expressing interneurons in the anterior insular cortex contribute to sensory processing to regulate adaptive behavior. Cell Rep. 39(9):110893. doi: 10.1016/j.celrep.2022.110893.
⇒it shows that VIP-expressing interneurons in the anterior insular cortex contribute to the detection and attribution of stimulus salience. - Kasugai Y., Vogel E., Hörtnagl H., Schönherr S., Paradiso E., Hauschild M., Göbel G., Milenkovic I., Peterschmitt Y., Tasan T., Sperk G., Shigemoto R., Sieghart W., Singewald N., Lüthi A., Ferraguti F.* (2019) Structural and functional remodeling of amygdala GABAergic synapses in associative fear learning. Neuron 104(4):781-794.e4. doi: 10.1016/j.neuron.2019.08.013.
⇒it demonstrates that GABAergic synapses in the basolateral amygdala undergo structural and functional plasticity during fear and extinction learning.
* corresponding author.
