Cortical Microcircuits in Schizophrenia - The Dopamine Hypothesis Revisited

Strong evidence exists for disturbed functional connectivity of cortical microcircuits--particularly of prefrontal cortex. Dopamine, long implicated in antipsychotic drug effects, is crucially involved in optimizing signal-to-noise ratio of local cortical micro-circuits. This action of dopamine is achieved by means of D1- and D2-receptor-mediated effects on pyramidal and local circuit neurons, which mediate recurrent inhibition and thus contribute to the stability of cortical representations of external and internal stimuli. In schizophrenia, a diminished cortical dopamine D1/D2 activation ratio--in concert with altered GABAergic and glutamatergic transmission--appear to critically interfere with this process.