• Research Project: linking glutamatergic and dopaminergic theories of schizophrenia

NB DIAZ, JE BELFORTE

Cordoba

Congreso; Segunda Reunion Anula Taller-SAN; 2010

For years, the dopaminergic hypothesis has dominated theories of schizophrenia. Recently, an alternative hypothesis proposes a cortical interneuron disturbance, due to NMDA receptor hypofunction, as a primary event in the physiopathology of the disorder. Supporting this theory, we have recently shown that ablation of NMDA receptors exclusively in corticolimbic interneurons of transgenic mice results in histological, behavioral and electrophysiological phenotypes compatible with a schizophrenia-like syndrome. Several phenotypes observed in the mutants (like novelty-induced hyperactivity, and working memory deficits) may result from a deregulation of the dopaminergic system. This project is aimed to determine the functional impact of early postnatal interneuron manipulation on corticolimbic control of the dopaminergic system. We speculate that the increased cortical activity observed in adult mutants results in abnormal control of the ventral tegmental area (VTA). To test this we will quantify behavioral-induced changes in immediate early gene expression in the VTA, perform electrophysiological recordings to explore cortical-VTA connectivity, and conduct pharmacological manipulations. We expect to provide a link between glutamatergic and dopaminergic theories of schizophrenia.