Uwe Rudolph, M.D.
Professor of Psychiatry
McLean Hospital, Mail stop 145
115 Mill Street
Belmont, MA 02478
Visit my lab page here.
Our lab is developing and studying genetic mouse models relevant for pathophysiology and treatment of psychiatric disorders. 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 the molecular substrates for the regulation of vigilance, anxiety, muscle tension, epileptogenic activity, sensorimotor gating, and memory function.
Using knock-in point mutations in mice, we were able to demonstrate that anxiolytic and sedative actions of benzodiazepines like diazepam can be pharmacologically separated, which is of relevance for drug development. We have generated “floxed” alleles of GABAA receptor subunit genes which allow to ablate the respective subunit in a subregion-specific manner, e.g. in hippocampal subregions or the amygdala, either via a cross with cre transgenic mice or via stereotaxic injection of cre-expressing viruses into defined brain regions. These animal models will be analyzed using biochemical, morphological and behavioral methods, and electrophysiological analysis is being performed by collaborating laboratories. Current projects focus on the regulation of anxiety, reward, depression as well as cognition by subsets of GABAA receptors. We also plan to use optogenetic techniques which would allow us to modulate the activity of a specific subset of neurons in a reversible fashion to elucidate their functions in different stages of behavioral paradigms, e.g. acquisition, consolidation, retrieval and extinction of memory. The identification of functions of individual GABAA receptor subtypes is envisioned to enhance our understanding of processes underlying central nervous system function and to lead to novel therapeutic strategies for the treatment of anxiety, psychotic, memory and mood disorders.
We also plan to generate mouse models with copy number variations (deletions and duplications) that have been shown to be risk factors for schizophrenia and autism in humans by chromosome engineering in order to be able to study the neurobiological role of such structural genomic variants.
For a complete listing of publications click here.
Last Update: 2/5/2014