Distinct prefrontal cortical regions negatively regulate evoked activity in nucleus accumbens subregions

Deficits in prefrontal cortical activity are consistent observations in a number of psychiatric diseases with two major regions consistently implicated being the medial prefrontal cortex (mPFC) and orbitofrontal cortex (OFC), regions that carry out independent, but complementary forms of cognitive processing in changing environmental conditions. Information from the prefrontal cortex is integrated in the nucleus accumbens (NAc) to guide goal-directed behaviour. Anatomical studies have demonstrated that distinct prefrontal cortical regions provide an overlapping but distinct innervation of NAc subregions; however, how information from these distinct regions regulates NAc output has not been conclusively demonstrated. Here we demonstrate that, while neurons receiving convergent glutamatergic inputs from the mPFC and OFC have a synergistic effect on single-spike firing, medium spiny neurons that receive a monosynaptic input from only one region are actually inhibited by activation of the complementary region. Therefore, the mPFC and OFC negatively regulate evoked activity within the lateral and medial regions of the NAc, respectively, and exist in a state of balance with respect to their influence on information processing within ventral striatal circuits.