Neuropharmacology of emotional systems
Prof. Dr. rer. nat. habil. M. Fendt
Emotions are important for the behavior of humans and animals. For example, the emotion fear helps to handle potentially dangerous situations. Pathological emotions in humans (e.g., depression, anxiety disorders) are highly prevalent and strongly linked to suffering.
Goal of our group is to improve our understanding of the neural basis of emotions. We are focused on the emotion fear in laboratory rodents within the following projects:
- Odor-induced fear
- Role of G-protein coupled receptors in innate and learned fear
- Neural mechanisms of event learning
- Role of emotions in narcoleptic episodes
Interest in performing a bachelor/master thesis or a lab rotation? Please contact us (Markus.Fendt@med.ovgu.de)
More detailed description of the projects:
Carnivore odor, e.g. samples of carnivore urine, induces defensive behavior in rodents. In collaboration with the laboratory of Steve Liberles (Harvard Medical School), we recently identified 2-phenylethylamine (PEA) as one component of carnivore urine which is innately recognized by rodents and induces defensive behavior (Ferrero et al., 2011). In contrast to other already described carnivore odors (e.g. trimethylthiazoline, propylthietane), PEA is not specific for only a few carnivore species but was found in the urine of all investigated carnivores so far. We further demonstrated that PEA is a very affine and specific activator of the olfactory receptor TAAR4 (trace-amine associated receptor, subtype 4). However, the neural pathway underlying PEA-induced fear behavior is unknown yet.
In the frame of a NeuroNetwork project, founded by the Center of Behavioral Brain Sciences, we started to identify and characterize the neural circuitry underlying PEA- and carnivore odor-induced fear behavior. Therefore, we are using methods from in vivo imaging, neuroanatomy, and behavioral pharmacology fields, as well as combinations of such methods. The NeuroNetwork project is a collaboration with the laboratories of Jürgen Goldschmidt (Leibniz Institute for Neurobiology) and Wolfgang D'Hanis (Institute for Neuroanatomy). Please see also our NeuroNetwork website.
In collaboration with Yasushi Kiyokawa (University of Tokyo), we started to investigate the neural mechanisms underlying alarm pheromone-induced defensive behavior in rats. Rats’ alarm pheromone is secreted from perianal glands and emitted in potentially dangerous situations. Our current research is focused on the role of the bed nucleus of the stria terminalis in alarm pheromone-induced defensive behavior.
Kerstin Wernecke, MSc Neurobiol (PhD project)
Tino Breitfeld (MD project)
Jessica Giese (MD project)
Breitfeld T, Bruning JEA, Inagaki H, Takeuchi Y, Kiyokawa Y & Fendt M (2015) Temporary inactivation of the anterior part of the bed nucleus of the stria terminalis blocks alarm pheromone-induced defensive behavior in rats. Front Neurosci 9: 321.
Wernecke KEA, Vincenz D, Storsberg S, D’Hanis W, Goldschmidt J & Fendt M (2015) Fox urine exposure induces avoidance behavior in rats and activates the amygdalar olfactory cortex. Behav Brain Res 279: 76-81.
Clinically established anxiolytic drugs are mainly working via the GABAergic, seretonergic and noradrenergic system. However, these mechanisms of action are connected to side effects and some patients are non-responsive. Therefore, there is a medical need to discover and to investigate new anxiolytic mechanisms of action. During the last decade, metabotropic glutamate receptors (mGluRs) and neuropeptide receptors came in the focus of fear research. Some of these receptors are meanwhile well investigates (e.g. mGluR2/3 agonists are clinically effective in Generalized Anxiety Disorders), others not.
Currently, we are especially interested in neuropeptide S. In a DFG-funded project, we explore the role of NPS and its receptor in animal models of pathological fear.
Małgorzata Kołodziejczyk, MSc (PhD project)
Josephine Thiele (MD project)
Radwa Khalil, MSc
Gee CE, Peterlik D, Neuhäuser C, Bouhelal R, Kaupmann K, Laue G, Uschold-Schmidt N, Feuerbach D, Zimmermann K, Ofner S, Cryan JF, van der Putten H, Fendt M, Vranesic I, Glatthar R& Flor PJ (2014) Blocking metabotropic glutamate receptor subtype 7 (mGlu7) via the venus flytrap domain (VFTD) inhibits amygdala plasticity, stress and anxiety-related behavior. J Biol Chem 289: 10975-10987.
Kahl E & Fendt M (2014) Injections of the somatostatin receptor type 2 agonist L-054,264 into the amygdala block expression but not acquisition of conditioned fear in rats. Behav Brain Res 265: 49-52.
During fear learning, stimuli which predict an aversive situation are learned. After such kind of learning, the learned stimulus alone is able to induce conditioned fear (which prepares the body for a potential further aversive situation). However, what happens if a stimulus is present at the end of an aversive situation? Recent research suggests that such stimuli elicit behaviors (e.g., approach behavior) indicating “conditioned relief”. A very similar learning phenomenon is safety learning. Here, animals and humans learn that a stimulus predicts the absence of an aversive event.
We investigate these phenomenona in rodents. We found that the acoustic startle response (which is used as a physiological measure of emotions) is strongly attenuated after relief and safety conditioning. Furthermore we showed that the nucleus accumbens, a part of the brain reward system, is important for conditioned relief but not for safety learning. Our future research shall be focused on further characterizing conditioned relief and its neural basis.
Jorge R. Bergado-Acosta, Dr. rer. nat. (postdoc project)
Johann Bruning (MD project)
Sascha Purmann, MSc (MD project)
Gerber B, Yarali A, Diegelmann S, Wotjak CT, Pauli P& Fendt M (2014) Pain-relief learning in flies, rats, and man: Basic research and applied perspectives. Learn Mem 21: 232-252.
Mohammadi M & Fendt M (2015) Relief learning is dependent on NMDA receptor activation in the nucleus accumbens. Br J Pharmacol 172: 2419-2426.
Mohammadi M, Bergado-Acosta JR & Fendt M (2014) Relief learning is distinguished from safety learning by the requirement of the nucleus accumbens. Behav Brain Res 272: 40-45.
Narcolepsy is a sleep disorder with the main symptoms excessive daytime sleepiness and cataplexy. Cataplexy is a sudden loss of muscle tone which can be considered exclusive to this condition. Very often, these episodes of cataplexy are induced by strong emotions such as laughter, surprise, anxiety or anger.
The main pathophysiological aspect of narcolepsy is the loss of orexin neurons in lateral hypothalamus, a brain site which is crucial for several behavioral and homeostatic functions, including arousal (sleep/wake cycle). Orexin has been shown to activate monoaminergic neurons in wake-promoting sides of the brain, including noradrenaline, dopamine, serotonin, and histamine.
Goal of this project is to improve our understanding how narcoleptic symptoms are induced and how they potentially could be treated. To this aim, we use orexin-deficient mice, an established animal model of narcolepsy. Interestingly, orexin-deficient mice do not only express narcoleptic symptoms but also show changes in other behaviors, e.g. defensive behavior. Therefore, we also characterize the role of orexin in defensive behaviors.
Christian Schmidt, MSc Pharm (MD project)
Radwa Khalil, MSc
Leibiger J & Fendt M. (2014) Behavioral analysis of narcoleptic episodes in orexin-deficient mice. Behav Genet 44: 136-143.
Morawska MM, Buchi M & Fendt M (2011) Narcoleptic episodes in orexin-deficient mice are increased by both attractive and aversive odors. Behav Brain Res 222: 397-400.