Neuronal Plasticity

Neuronal Plasticity

Anxiety disorders such as post-traumatic stress disorder (PTSD), generalized anxiety disorder, specific and social phobias, panic disorder and agoraphobia belong to the most prevalent psychiatric disorders in Western societies with enormous individual and economic burden. The success of therapeutic intervention is limited, which may be due to the fact that our understanding of disease mechanisms is still in its infancy. Our research group has pioneered the establishment of mouse models of psychiatric diseases and emotional dysregulation. We also achieved major contributions regarding the neurobiology of the endocannabinoid system in development and extinction of exaggerated fear. In addition, we unraveled major factors of the interrelationship between anxiety and cognition.

Our studies combine in vivo electrophysiology, optogenetic and pharmacogenetic techniques, in vivo microdialysis, behavioral pharmacology, in vivo imaging (magnetic resonance spectroscopy, manganese-enhanced MRI), histochemical and molecular analyses in wild-type and mutant mice. Group members have a strong background in behavioral biology, psychology, pharmacology, psychiatry and electronics. Our main research topics are as follows:

A mouse model of PTSD – diagnostic categories, biological basis and therapeutic interventions

Using our mouse model, we identified brain structures and molecular mechanisms that underlie the formation and long-term maintenance of hyperarousal and exaggerated fear. Our studies are expected to lead to the development of novel therapeutic intervention strategies. In a translational aspect, we are closely collaborating with our Institute's Clinic.

As fear goes by – how to overcome phobic fear and generalized anxiety

On the basis of classical and operant conditioning, we work with mouse models of exposure-based therapies and study beneficial consequences of alterations in endocannabinoid and endovanilloid signaling. In addition, we employ in vivo imaging and optogenetic / pharmacogenetic tools to identify and validate brain circuits implicated in anxiety and fear.

Don’t panic – about panic attacks and agoraphobia

Surprisingly, little is known about the generation of panic attacks and the development and extinction of avoidance behavior, akin to agoraphobia. We combine safety learning procedures with pharmacological enhancement of endocannabinoid signaling and optogenetic / pharmacogenetic modulation of monoamine transmission to overcome panic- and agoraphobia-like symptoms in genetically modified mouse models. To increase the translational value and face validity of our studies, we frequently discuss our projects and results with clinicians from the Outpatient Clinic for Anxiety Disorders at our Institute.

Where am I – spatial navigation in mice with altered emotionality

We have recently established and validated the water cross-maze as a spatial learning task which allows us to differentiate between place (i.e. allocentric) and response (i.e. egocentric) learning strategies. Using such a behavioral task, we attempt to identify brain structures involved in different learning processes in vivo using different genetic mouse models. We also use mice with inbred extremes in anxiety-related behavior to gain insight into the interrelationship between anxiety and cognition. Importantly, we aim to ameliorate cognitive impairments by novel pharmacological means.

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