Intrinsic excitatory connections in the prefrontal cortex and the pathophysiology of schizophrenia

Working memory, a fundamental cognitive process that is disturbed in schizo phrenia, appears to depend upon the sustained activity of specific populati ons of neurons in the prefrontal cortex. Understanding the neural mechanism (s) that may contribute to the sustained activity of these neurons represen ts a critical step in predicting the types of alterations in prefrontal cir cuitry that may be present in schizophrenia, and in determining how such al terations may contribute to the cognitive symptoms of this disorder, This a rticle reviews recent findings which suggest that intrinsic horizontal conn ections among pyramidal neurons in layer 3 of the dorsolateral prefrontal c ortex may provide a critical anatomical substrate for working memory proces ses, and that alterations in these connections may account for the observat ions of disturbed working memory, adolescence-related onset of clinical fea tures, and certain pathological changes in the prefrontal cortex of subject s with schizophrenia. (C) 2000 Elsevier Science Inc.