Brain Disorders and Novel Therapeutics

Using the power of genetic intervention, a strategy is illustrated which permits new insights into the pathobiology of brain diseases and the discovery of new therapeutic strategies. Brain function is based on a delicate balance between excitory and inhibitory neurotransmission. Selective circuits of GABAergic inhibitory transmission were targeted by introducing point mutations in defined GABAA receptor subtype genes in mice (knock-in strategy). New behavioural phenotypes were generated which reflect various brain disorders. In addition, novel drug targets were identified for the treatment of anxiety disorders, sleep disturbances, memory deficits, and schizophrenia.