Model generation and testing to probe neural circuitry in the cingulate cortex of postmortem schizophrenic brain

Abstract

In the past decade, there has been increased interest in whether discreet alterations of neural circuitry might play a role in the pathophysiology of schizophrenia. In the absence of a readily identifiable histopathology, a variety of sophisticated neurobiological approaches is being applied to the study of this disorder. In one series of investigations, subtle abnormalities have been detected in the anterior cingulate cortex-layer II (ACCx-II) of schizophrenia patients. One of these studies suggested a reduction of nonpyramidal neurons in schizophrenia patients, and it was postulated that this change could give rise to a relative increase of dopaminergic inputs to the remaining gamma-aminobutyric acid (GABA) cells. Although empiric evidence in support of this hypothesis was obtained, a subsequent post hoc analysis, described in this report, has suggested that this change could have occurred irrespective of whether GABA cells are reduced in number. A shift of cortical dopamine afferents from pyramidal to nonpyramidal neurons in ACCx-II seems to provide a more plausible explanation for such a "miswiring." These findings support critical use of model generation and testing as powerful tools for unraveling the nature of altered neural circuitry in postmortem schizophrenic brain.