The Rudolph Lab is developing and studying genetic mouse models relevant for pathophysiology and treatment of psychiatric disorders using molecular biological, biochemical, morphological, optogenetic, chemogenetic and behavioral methods. A major focus is on synaptic and extrasynaptic inhibition in the CNS, specifically the physiological and pharmacological functions of inhibitory neurotransmission viaGABAA receptor subtypes and of excitatory neurotransmission via NMDA receptors.
GABAA receptors are molecular substrates for the regulation of vigilance, anxiety, fear, sensorimotor gating, and learning and memory. Using knock-in point mutations in mice, we were able to demonstrate that anxiolytic and sedative actions of benzodiazepines like diazepam are mediated by distinct GABAA receptor subtypes and can thus be pharmacologically separated, which is of relevance for drug development (U. Rudolph et al., Nature 1999;401:796-800; K. Low et al., Science 2000;290:131-134, U. Rudolph and F. Knoflach, Nature Reviews Drug Discovery 2011;10:685-697). Using conditional gene targeting, we found that anxiety and fear are modulated by distinct intrahippocampal circuits, and that tonic inhibitory control of the dentate gyrus granule cells reduces memory interference (E. Engin et al., Journal of Neuroscience 2015;35:13698-13712; E. Engin et al., eLife 2016;5:e14120; Engin et al., Trends in Pharmacological Sciences 2018;39:710-732). We also interested in the role of specific GABAA receptors in the response to chronic social defeat stress and thus potentially for the development of depression.
Our Principal Investigator is Uwe Rudolph.
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