PiN Faculty Member - Uwe Rudolph, MD

Uwe Rudolph, MD

Professor of Psychiatry

Lab of Genetic Neuropharmacology
McLean Hospital, Mail stop 145
115 Mill Street
Belmont, MA 02478
Tel: 617-855-2088
Fax: 617-855-2012
Email: urudolph@mclean.harvard.edu
Visit my lab page here.



Our 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 GABAA receptor subtypes. 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. 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.

Current projects focus on investigating whether modulation of specific GABAA receptor subtypes can elicit fast antidepressant-like effects and on the chemogenetic identification of neuronal cell types and circuits required for such a response, and on the optogenetic investigation of the role of defined hippocampal projections in the modulation of anxiety and fear. We have also generated multiple copy number variation (CNV) mouse models mimicking structural genomic variation found in schizophrenia, bipolar disorder and autism using trans-allelic recombination, and are investigating the neurobiological basis by which these CNVs increase the risk for neurodevelopmental disorders. CNVs are relatively rare mutations with large effect sizes, and it is expected that their analysis leads to the identification and characterization of core pathophysiological pathways of neurodevelopmental disorders.



Last Update: 8/22/2017



Publications

For a complete listing of publications click here.

 


 



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